This document reviews different insulin initiation regimens for patients with type 2 diabetes. It discusses starting patients on basal insulin like NPH or long-acting analogues like glargine or detemir, administered once or twice daily. Insulin can be initiated at 10 units/day or 0.1-0.2 units/kg/day and titrated up every 1-2 weeks based on fasting plasma glucose levels. Premixed insulins are also reviewed for initiation, starting at 10 units/once daily or 0.3-0.5 units/kg/day. A basal-bolus regimen adding rapid-acting insulin before meals is discussed for intensifying treatment if targets are not met with basal insulin alone
This document discusses techniques for achieving optimal treatment goals for diabetes care. It outlines:
1. Targets such as glucose control, comprehensive care addressing medical, psychological, and social needs, and achieving "euthemic euglycemia" or optimal blood sugar control and mental well-being.
2. Techniques including pharmacotherapy, therapeutic patient education, behavioral modification, bariatric surgery, and managing diet, exercise, and stress.
3. Specific approaches are discussed like the "therapeutic sixer" targeting efficacy and safety, and use of DPP-4 inhibitors to provide glycemic control while reducing risks of hypoglycemia and weight gain.
1. SGLT-2 inhibitors lower blood glucose by inhibiting glucose reabsorption in the kidneys, increasing glucose excretion in the urine.
2. Empagliflozin, a SGLT-2 inhibitor, lowers blood glucose by reducing the renal threshold for glucose, increasing urinary glucose excretion.
3. In clinical trials, empagliflozin significantly reduced hemoglobin A1c, fasting plasma glucose, and post-prandial plasma glucose when used as monotherapy or added to other antihyperglycemic medications, with a low risk of hypoglycemia.
Ueda2016 symposium - basal plus & basal bolus - lobna el toonyueda2015
This document discusses the stepwise intensification of insulin therapy in the management of type 2 diabetes mellitus (T2DM). It recommends starting with basal insulin as the first step, such as intermediate- or long-acting insulin added to oral antidiabetic drugs. Basal insulin is effective at improving fasting plasma glucose and provides an easy and generally safe treatment approach with a low risk of hypoglycemia. The document reviews the advantages of different basal insulin options and provides guidelines for initiating and titrating a basal insulin regimen to optimize glycemic control in patients with T2DM.
This document summarizes a presentation given by Cathy Breen on type 2 diabetes. The key points are:
1) Type 2 diabetes is reaching pandemic levels globally with over 430 million predicted cases by 2030. Major risk factors driving this include obesity, lack of physical activity, and unhealthy diet.
2) The costs of type 2 diabetes are substantial, both in terms of decreased quality of life due to complications and comorbidities, as well as monetary healthcare costs.
3) Lifestyle interventions focused on modest weight loss through calorie reduction and increased physical activity have been shown to significantly improve outcomes of type 2 diabetes such as HbA1c and weight. Dietitians are uniquely qualified to lead these
The SAVOR-TIMI 53 trial investigated the cardiovascular outcomes of adding saxagliptin to standard care in 16,492 patients with type 2 diabetes and high cardiovascular risk over a median of 2.1 years. The primary endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 11.3% of the saxagliptin group and 11.8% of the placebo group, demonstrating saxagliptin's noninferiority. However, hospitalization for heart failure occurred more frequently in the saxagliptin group. The TECOS trial of 14,671 patients with type 2 diabetes, established cardiovascular disease, and inadequate glycemic control investigated adding sitagliptin or placebo to
The document discusses type 2 diabetes mellitus (T2DM) and strategies for achieving glycemic targets. It notes the increasing complexity of T2DM management given the variety of treatment options available and concerns about intensive control. The document summarizes guidelines recommending individualized glycemic targets and avoidance of hypoglycemia. It also reviews studies showing that sitagliptin added to metformin or insulin therapy was effective at lowering blood sugar levels compared to other agents, with a lower risk of hypoglycemia and weight gain.
This document summarizes the key points from a scientific seminar on diabetes management and glycemic control. It discusses:
1) The growing problem of diabetes worldwide, with 382 million current cases projected to rise to 592 million by 2035.
2) Glycemic control, as measured by HbA1c levels, remains poor globally. The average HbA1c ranges from 7-10% depending on the country.
3) Treatment with basal-bolus insulin regimens using rapid-acting insulin analogs can help improve post-prandial glycemic control compared to regular human insulin, but hypoglycemia remains a barrier to achieving targets.
Ueda2015 lilly.the art of insulin dr.mesbah sayedueda2015
This document discusses the treatment of a 52-year-old patient with type 2 diabetes who has an HbA1c of 9.4% despite treatment with oral medications. It considers adding insulin therapy to help control the patient's blood glucose levels and reach treatment targets. Specifically, it compares the effectiveness of premixed insulin versus basal insulin when initiating insulin in type 2 diabetes patients. A study is summarized that found premixed insulin administered twice daily in combination with metformin was more effective at reducing HbA1c and post-prandial blood glucose compared to a basal insulin administered once daily plus metformin. The document advocates for patient-centered treatment approaches and discusses factors to consider when choosing between premixed versus basal-bolus insulin reg
This document discusses techniques for achieving optimal treatment goals for diabetes care. It outlines:
1. Targets such as glucose control, comprehensive care addressing medical, psychological, and social needs, and achieving "euthemic euglycemia" or optimal blood sugar control and mental well-being.
2. Techniques including pharmacotherapy, therapeutic patient education, behavioral modification, bariatric surgery, and managing diet, exercise, and stress.
3. Specific approaches are discussed like the "therapeutic sixer" targeting efficacy and safety, and use of DPP-4 inhibitors to provide glycemic control while reducing risks of hypoglycemia and weight gain.
1. SGLT-2 inhibitors lower blood glucose by inhibiting glucose reabsorption in the kidneys, increasing glucose excretion in the urine.
2. Empagliflozin, a SGLT-2 inhibitor, lowers blood glucose by reducing the renal threshold for glucose, increasing urinary glucose excretion.
3. In clinical trials, empagliflozin significantly reduced hemoglobin A1c, fasting plasma glucose, and post-prandial plasma glucose when used as monotherapy or added to other antihyperglycemic medications, with a low risk of hypoglycemia.
Ueda2016 symposium - basal plus & basal bolus - lobna el toonyueda2015
This document discusses the stepwise intensification of insulin therapy in the management of type 2 diabetes mellitus (T2DM). It recommends starting with basal insulin as the first step, such as intermediate- or long-acting insulin added to oral antidiabetic drugs. Basal insulin is effective at improving fasting plasma glucose and provides an easy and generally safe treatment approach with a low risk of hypoglycemia. The document reviews the advantages of different basal insulin options and provides guidelines for initiating and titrating a basal insulin regimen to optimize glycemic control in patients with T2DM.
This document summarizes a presentation given by Cathy Breen on type 2 diabetes. The key points are:
1) Type 2 diabetes is reaching pandemic levels globally with over 430 million predicted cases by 2030. Major risk factors driving this include obesity, lack of physical activity, and unhealthy diet.
2) The costs of type 2 diabetes are substantial, both in terms of decreased quality of life due to complications and comorbidities, as well as monetary healthcare costs.
3) Lifestyle interventions focused on modest weight loss through calorie reduction and increased physical activity have been shown to significantly improve outcomes of type 2 diabetes such as HbA1c and weight. Dietitians are uniquely qualified to lead these
The SAVOR-TIMI 53 trial investigated the cardiovascular outcomes of adding saxagliptin to standard care in 16,492 patients with type 2 diabetes and high cardiovascular risk over a median of 2.1 years. The primary endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 11.3% of the saxagliptin group and 11.8% of the placebo group, demonstrating saxagliptin's noninferiority. However, hospitalization for heart failure occurred more frequently in the saxagliptin group. The TECOS trial of 14,671 patients with type 2 diabetes, established cardiovascular disease, and inadequate glycemic control investigated adding sitagliptin or placebo to
The document discusses type 2 diabetes mellitus (T2DM) and strategies for achieving glycemic targets. It notes the increasing complexity of T2DM management given the variety of treatment options available and concerns about intensive control. The document summarizes guidelines recommending individualized glycemic targets and avoidance of hypoglycemia. It also reviews studies showing that sitagliptin added to metformin or insulin therapy was effective at lowering blood sugar levels compared to other agents, with a lower risk of hypoglycemia and weight gain.
This document summarizes the key points from a scientific seminar on diabetes management and glycemic control. It discusses:
1) The growing problem of diabetes worldwide, with 382 million current cases projected to rise to 592 million by 2035.
2) Glycemic control, as measured by HbA1c levels, remains poor globally. The average HbA1c ranges from 7-10% depending on the country.
3) Treatment with basal-bolus insulin regimens using rapid-acting insulin analogs can help improve post-prandial glycemic control compared to regular human insulin, but hypoglycemia remains a barrier to achieving targets.
Ueda2015 lilly.the art of insulin dr.mesbah sayedueda2015
This document discusses the treatment of a 52-year-old patient with type 2 diabetes who has an HbA1c of 9.4% despite treatment with oral medications. It considers adding insulin therapy to help control the patient's blood glucose levels and reach treatment targets. Specifically, it compares the effectiveness of premixed insulin versus basal insulin when initiating insulin in type 2 diabetes patients. A study is summarized that found premixed insulin administered twice daily in combination with metformin was more effective at reducing HbA1c and post-prandial blood glucose compared to a basal insulin administered once daily plus metformin. The document advocates for patient-centered treatment approaches and discusses factors to consider when choosing between premixed versus basal-bolus insulin reg
ABSTRACT
Over the last decade, diabetes mellitus has emerged as an important clinical and public health
problem throughout the world. The aim of the study is perceive the Potentiality of a newer oral
Antihyperglycemic combination therapy over conventional therapy in type 2 diabetes. The
prospective study was conducted over a period of six months in the department of Medicine,
Guntur City Hospital. The prevalence of type2 diabetes was high in male 65.79 % than female
34.21%. Majority of the patients (23.68 %) belonged to age group of 51–55 years. Majority of
patients (55.26%) having a family history of Diabetes. Majority of patients receiving Combination
of Glibenclamide + Metformin (60.53%), evaluated for effect on FPG for both combinations. The
mean changes in FPG were noted. In the same way effect on HbA1c also noted. Mean changes in
for every month HbA1c will be noted. Our study reveals that Combination therapy with Metformin
plus Glimepiride is more effective than Glibenclamide plus Metformin; in improving glycemic
control in type 2 diabetes, while also allowing a reduction of the dosage of each drug.
Optimising glycaemic control and body weightsimplyweight
This Slideshow gives you insight on the Mix50 insulin
For more information please visit
http://www.simplyweight.co.uk
Articles
http://www.simplyweight.co.uk/articles/
Videos
http://www.simplyweight.co.uk/video/
Blogs
http://simplyweight.co.uk/blogs/
Forum
http://www.simplyweight.co.uk/forum/forum.php
Contact Us
http://www.simplyweight.co.uk/how-to-contact-us/
This document discusses challenges with insulin therapy for primary care and provides solutions. It notes that insulin reduces A1C more than oral agents, with insulin reducing A1C by at least 2.5%. The ADA-EASD consensus recommends starting insulin first for patients with an A1C over 10%, fasting blood sugar over 250 mg/dl, or random blood sugars consistently over 300 mg/dl. Treating fasting hyperglycemia with basal insulin can lower overall 24-hour plasma glucose levels. Insulin glargine reduces risks of nocturnal hypoglycemia compared to NPH insulin. Studies also found patients were able to remain on insulin glargine plus oral drugs for an extended period without needing intensified treatment.
This document discusses barriers to insulin therapy. It notes that while diabetes guidelines recommend tight glycemic control through insulin therapy, few patients actually achieve target HbA1c levels. Barriers include limitations among healthcare providers in providing education on proper insulin administration techniques, as well as patient challenges like fear of hypoglycemia, weight gain, and the perceived complexity of insulin treatment. Overcoming these barriers through education on insulin products like Insuman, which can be easily resuspended to ensure accurate dosing, and reusable insulin pens like AllStar, which are easy for patients to use correctly, may help improve adherence to insulin regimens.
Dipeptidyl peptidase inhibitors(DPP-IV): A deep insightRxVichuZ
This presentation deals with DPP-IV inhibitors, that are implicated for use in diabetes mellitus. Generalized pharmacology, including a precise insight into individual drugs have been elucidated.
Ueda2015 prevention of cv diseade in dm dr.yehia kishkueda2015
1) Cardiovascular disease and type 2 diabetes place a huge burden on health in Egypt, being among the top causes of death. Intensive control of blood sugar, blood pressure, and lipids is effective for secondary prevention of CVD in diabetes patients.
2) Primary prevention approaches target prediabetes through lifestyle changes like weight loss and exercise to prevent progression to diabetes, along with screening and treatment of other risk factors.
3) The DPP clinical trial showed that lifestyle interventions can reduce the risk of developing diabetes by 58% in those with prediabetes. Intensive management of multiple risk factors is key to reducing complications in those with diabetes or CVD.
1) Gliptins like vildagliptin have less risk of hypoglycemia and weight gain compared to sulfonylureas.
2) Vildagliptin has shown beneficial effects on blood pressure and lipid levels.
3) Meta-analyses of clinical trials show that gliptins like vildagliptin have no increased cardiovascular risk compared to other antidiabetic drugs, and may have cardio-protective effects.
Clinical Improvement Proceeds Glycemic Homeostasis After Duodenal-jejunal Byp...George S. Ferzli
This document discusses the effects of duodenal-jejunal bypass surgery on non-obese patients with type 2 diabetes. It summarizes that clinical improvement in diabetes indicators like blood glucose and HbA1c levels precedes significant weight loss after the surgery. The surgery is believed to directly impact diabetes through hormonal changes and rearrangement of gastrointestinal anatomy, rather than just indirectly through weight loss. Specifically, bypassing the duodenum and proximal jejunum has been shown to control type 2 diabetes in non-obese animal models by altering gut hormone secretion like GLP-1.
- Type 2 diabetes is associated with increased risk of cardiovascular disease. Up to 80% of patients with diabetes develop macrovascular disease.
- Guidelines from the ADA and EASD recommend early use of combination therapies to control blood sugar levels tightly and avoid clinical inertia.
- Saxagliptin/Metformin fixed dose combination is recommended as it provides 24-hour glycemic control with once daily dosing through complementary mechanisms of action without increasing hypoglycemia risk. It has shown sustained efficacy over 4 years in clinical trials.
On DPP-Inhibitor ,case study on Linagliptin,Safe and affective class of drug for Management of Type II Diabetes as Monotherapy and add on therapy with OHA and Insulin,It can be added to SGLT2 Inhibitor also.
Achieving Hba1c targets: Strategies For Initiating and Intensifying Diabetes ...Nemencio Jr
This module highlights the appropriate HbA1c targets that reduce microvascular and macrovascular complications in appropriate populations and how to safely achieve them with current anti-hyperglycemic agents
1. The document summarizes a clinical audit of exenatide use in diabetes patients at a hospital outpatient department. It assessed adherence to guidelines for prescribing exenatide and outcomes in patients prescribed the drug.
2. The audit found some criteria for starting exenatide were met according to guidelines but many patients were already on insulin when prescribed it. Outcomes varied but most lost weight; about half saw improved blood sugar levels.
3. Documentation of prescribing and patient education needs improvement. Follow-up appointments were usually arranged appropriately though the drug had only been used short-term for most patients.
Safety and Efficacy of Sulfonylurea Drugs in Type 2 Diabetes MellitusApollo Hospitals
In subjects with type 2 diabetes mellitus, glycemic control will be established while patients use sulfonylurea drugs during the course of the disease. However, data regarding direct comparison between various sulfonylureas in this regard are lacking. Weight loss usually improves blood glucose levels for people with type 2 diabetes. However, many also need oral medications or insulin.
Dpp4i vs sglt2 inhibitors against the motionSujoy Majumdar
A debate showing why SGLT2 inhibitors have not have a major advantage over DPP4 inhibitors as the next add on drug after Metformin in the management of Type 2 Diabetes
1. Metformin is effective for treating type 2 diabetes as monotherapy or in combination with other agents by lowering glucose production and increasing insulin sensitivity.
2. It has a good safety profile with minimal hypoglycemia risk and is weight neutral. Long term use is associated with possible cardiovascular benefits.
3. While the risk of lactic acidosis is very low, metformin use should be monitored in patients with chronic kidney disease, especially those with eGFR <30 mL/min/1.73 m2.
- DPP-4 inhibitors like vildagliptin work by inhibiting the DPP-4 enzyme, which helps increase levels of incretin hormones like GLP-1. This can improve insulin secretion and suppress glucagon secretion from the islet cells.
- A clinical trial found that adding vildagliptin to metformin therapy produced greater reductions in HbA1c and fasting plasma glucose compared to metformin alone. It also enhanced beta-cell function and improved postprandial glucose levels.
- Initial combination therapy of vildagliptin and metformin was effective across a range of baseline HbA1c levels, with more patients achieving an HbA1c under 7% compared to sulf
Ueda2016 symposium -t2 dm management - lobna el toonyueda2015
Sitagliptin improves glycemic control in a glucose-dependent manner by increasing concentrations of active incretin hormones like GLP-1. It targets the metabolic defects of type 2 diabetes by improving markers of beta-cell function, reducing hepatic glucose overproduction, and having insulin-sensitizing properties. Studies show sitagliptin is associated with a lower risk of hypoglycemia and less weight gain compared to sulfonylureas when added to metformin. It also provides durable glycemic control with a lower risk of requiring additional antihyperglycemic medications over time.
Exenatide is a synthetic version of exendin-4, a peptide found in the saliva of the Gila monster lizard. It mimics the effects of the human incretin hormone GLP-1, leading to glucose-dependent insulin secretion and suppression of glucagon secretion. Exenatide is administered via subcutaneous injection twice daily. It effectively lowers blood glucose levels when used in combination with metformin and/or sulfonylureas. Common side effects include nausea and vomiting.
The document discusses the role of the kidney in glucose regulation. The kidney releases glucose into the bloodstream via gluconeogenesis in the renal cortex and takes up glucose from the blood for energy in the renal medulla. The kidney also reabsorbs glucose from the proximal convoluted tubule. SGLT2 inhibitors like canagliflozin, dapagliflozin, and empagliflozin work by inhibiting glucose reabsorption in the kidney, thereby increasing glucose excretion and lowering blood glucose levels. They provide glycemic control with a low risk of hypoglycemia when used alone but a higher risk when combined with insulin or insulin secretagogues. Side effects include genital infections, urinary
- Insulin therapy is eventually required for many patients with type 2 diabetes as pancreatic function continues to decline over time. Basal insulin therapy is usually initiated first to control fasting blood glucose, with the addition of prandial insulin if A1C levels remain high.
- Guidelines recommend starting basal insulin when A1C is ≥8.5% or if the total daily basal insulin dose nears 1 unit/kg/day. Prandial insulin should be added if the daily basal dose exceeds 0.5 units/kg/day or to control post-meal blood glucose excursions.
- Insulin regimens can include basal-bolus therapy with long or intermediate acting basal insulin plus rapid-acting pr
Intensification Options after basal Insulin RevisitedUsama Ragab
Intensification Options revisited
By Dr. Usama Ragab Youssif
Add an OAD
Add a short-acting insulin at mealtime
Switch to premixed insulins
Novel insulin combinations
Basal insulin/GLP-1 RA combinations
This document provides treatment guidelines for diabetes mellitus. It discusses the types of diabetes, symptoms, complications, goals of treatment, and treatment options. Treatment involves lifestyle changes like diet and exercise. Pharmacological treatment starts with metformin for type 2 diabetes and insulin for type 1 diabetes. Insulin therapy is initiated at 0.4-1.0 units/kg/day for type 1 diabetes. Additional agents may be added if blood sugar levels remain uncontrolled. The goal of treatment is to achieve a hemoglobin A1c level below 7% through lifestyle management and medication adjustments.
ABSTRACT
Over the last decade, diabetes mellitus has emerged as an important clinical and public health
problem throughout the world. The aim of the study is perceive the Potentiality of a newer oral
Antihyperglycemic combination therapy over conventional therapy in type 2 diabetes. The
prospective study was conducted over a period of six months in the department of Medicine,
Guntur City Hospital. The prevalence of type2 diabetes was high in male 65.79 % than female
34.21%. Majority of the patients (23.68 %) belonged to age group of 51–55 years. Majority of
patients (55.26%) having a family history of Diabetes. Majority of patients receiving Combination
of Glibenclamide + Metformin (60.53%), evaluated for effect on FPG for both combinations. The
mean changes in FPG were noted. In the same way effect on HbA1c also noted. Mean changes in
for every month HbA1c will be noted. Our study reveals that Combination therapy with Metformin
plus Glimepiride is more effective than Glibenclamide plus Metformin; in improving glycemic
control in type 2 diabetes, while also allowing a reduction of the dosage of each drug.
Optimising glycaemic control and body weightsimplyweight
This Slideshow gives you insight on the Mix50 insulin
For more information please visit
http://www.simplyweight.co.uk
Articles
http://www.simplyweight.co.uk/articles/
Videos
http://www.simplyweight.co.uk/video/
Blogs
http://simplyweight.co.uk/blogs/
Forum
http://www.simplyweight.co.uk/forum/forum.php
Contact Us
http://www.simplyweight.co.uk/how-to-contact-us/
This document discusses challenges with insulin therapy for primary care and provides solutions. It notes that insulin reduces A1C more than oral agents, with insulin reducing A1C by at least 2.5%. The ADA-EASD consensus recommends starting insulin first for patients with an A1C over 10%, fasting blood sugar over 250 mg/dl, or random blood sugars consistently over 300 mg/dl. Treating fasting hyperglycemia with basal insulin can lower overall 24-hour plasma glucose levels. Insulin glargine reduces risks of nocturnal hypoglycemia compared to NPH insulin. Studies also found patients were able to remain on insulin glargine plus oral drugs for an extended period without needing intensified treatment.
This document discusses barriers to insulin therapy. It notes that while diabetes guidelines recommend tight glycemic control through insulin therapy, few patients actually achieve target HbA1c levels. Barriers include limitations among healthcare providers in providing education on proper insulin administration techniques, as well as patient challenges like fear of hypoglycemia, weight gain, and the perceived complexity of insulin treatment. Overcoming these barriers through education on insulin products like Insuman, which can be easily resuspended to ensure accurate dosing, and reusable insulin pens like AllStar, which are easy for patients to use correctly, may help improve adherence to insulin regimens.
Dipeptidyl peptidase inhibitors(DPP-IV): A deep insightRxVichuZ
This presentation deals with DPP-IV inhibitors, that are implicated for use in diabetes mellitus. Generalized pharmacology, including a precise insight into individual drugs have been elucidated.
Ueda2015 prevention of cv diseade in dm dr.yehia kishkueda2015
1) Cardiovascular disease and type 2 diabetes place a huge burden on health in Egypt, being among the top causes of death. Intensive control of blood sugar, blood pressure, and lipids is effective for secondary prevention of CVD in diabetes patients.
2) Primary prevention approaches target prediabetes through lifestyle changes like weight loss and exercise to prevent progression to diabetes, along with screening and treatment of other risk factors.
3) The DPP clinical trial showed that lifestyle interventions can reduce the risk of developing diabetes by 58% in those with prediabetes. Intensive management of multiple risk factors is key to reducing complications in those with diabetes or CVD.
1) Gliptins like vildagliptin have less risk of hypoglycemia and weight gain compared to sulfonylureas.
2) Vildagliptin has shown beneficial effects on blood pressure and lipid levels.
3) Meta-analyses of clinical trials show that gliptins like vildagliptin have no increased cardiovascular risk compared to other antidiabetic drugs, and may have cardio-protective effects.
Clinical Improvement Proceeds Glycemic Homeostasis After Duodenal-jejunal Byp...George S. Ferzli
This document discusses the effects of duodenal-jejunal bypass surgery on non-obese patients with type 2 diabetes. It summarizes that clinical improvement in diabetes indicators like blood glucose and HbA1c levels precedes significant weight loss after the surgery. The surgery is believed to directly impact diabetes through hormonal changes and rearrangement of gastrointestinal anatomy, rather than just indirectly through weight loss. Specifically, bypassing the duodenum and proximal jejunum has been shown to control type 2 diabetes in non-obese animal models by altering gut hormone secretion like GLP-1.
- Type 2 diabetes is associated with increased risk of cardiovascular disease. Up to 80% of patients with diabetes develop macrovascular disease.
- Guidelines from the ADA and EASD recommend early use of combination therapies to control blood sugar levels tightly and avoid clinical inertia.
- Saxagliptin/Metformin fixed dose combination is recommended as it provides 24-hour glycemic control with once daily dosing through complementary mechanisms of action without increasing hypoglycemia risk. It has shown sustained efficacy over 4 years in clinical trials.
On DPP-Inhibitor ,case study on Linagliptin,Safe and affective class of drug for Management of Type II Diabetes as Monotherapy and add on therapy with OHA and Insulin,It can be added to SGLT2 Inhibitor also.
Achieving Hba1c targets: Strategies For Initiating and Intensifying Diabetes ...Nemencio Jr
This module highlights the appropriate HbA1c targets that reduce microvascular and macrovascular complications in appropriate populations and how to safely achieve them with current anti-hyperglycemic agents
1. The document summarizes a clinical audit of exenatide use in diabetes patients at a hospital outpatient department. It assessed adherence to guidelines for prescribing exenatide and outcomes in patients prescribed the drug.
2. The audit found some criteria for starting exenatide were met according to guidelines but many patients were already on insulin when prescribed it. Outcomes varied but most lost weight; about half saw improved blood sugar levels.
3. Documentation of prescribing and patient education needs improvement. Follow-up appointments were usually arranged appropriately though the drug had only been used short-term for most patients.
Safety and Efficacy of Sulfonylurea Drugs in Type 2 Diabetes MellitusApollo Hospitals
In subjects with type 2 diabetes mellitus, glycemic control will be established while patients use sulfonylurea drugs during the course of the disease. However, data regarding direct comparison between various sulfonylureas in this regard are lacking. Weight loss usually improves blood glucose levels for people with type 2 diabetes. However, many also need oral medications or insulin.
Dpp4i vs sglt2 inhibitors against the motionSujoy Majumdar
A debate showing why SGLT2 inhibitors have not have a major advantage over DPP4 inhibitors as the next add on drug after Metformin in the management of Type 2 Diabetes
1. Metformin is effective for treating type 2 diabetes as monotherapy or in combination with other agents by lowering glucose production and increasing insulin sensitivity.
2. It has a good safety profile with minimal hypoglycemia risk and is weight neutral. Long term use is associated with possible cardiovascular benefits.
3. While the risk of lactic acidosis is very low, metformin use should be monitored in patients with chronic kidney disease, especially those with eGFR <30 mL/min/1.73 m2.
- DPP-4 inhibitors like vildagliptin work by inhibiting the DPP-4 enzyme, which helps increase levels of incretin hormones like GLP-1. This can improve insulin secretion and suppress glucagon secretion from the islet cells.
- A clinical trial found that adding vildagliptin to metformin therapy produced greater reductions in HbA1c and fasting plasma glucose compared to metformin alone. It also enhanced beta-cell function and improved postprandial glucose levels.
- Initial combination therapy of vildagliptin and metformin was effective across a range of baseline HbA1c levels, with more patients achieving an HbA1c under 7% compared to sulf
Ueda2016 symposium -t2 dm management - lobna el toonyueda2015
Sitagliptin improves glycemic control in a glucose-dependent manner by increasing concentrations of active incretin hormones like GLP-1. It targets the metabolic defects of type 2 diabetes by improving markers of beta-cell function, reducing hepatic glucose overproduction, and having insulin-sensitizing properties. Studies show sitagliptin is associated with a lower risk of hypoglycemia and less weight gain compared to sulfonylureas when added to metformin. It also provides durable glycemic control with a lower risk of requiring additional antihyperglycemic medications over time.
Exenatide is a synthetic version of exendin-4, a peptide found in the saliva of the Gila monster lizard. It mimics the effects of the human incretin hormone GLP-1, leading to glucose-dependent insulin secretion and suppression of glucagon secretion. Exenatide is administered via subcutaneous injection twice daily. It effectively lowers blood glucose levels when used in combination with metformin and/or sulfonylureas. Common side effects include nausea and vomiting.
The document discusses the role of the kidney in glucose regulation. The kidney releases glucose into the bloodstream via gluconeogenesis in the renal cortex and takes up glucose from the blood for energy in the renal medulla. The kidney also reabsorbs glucose from the proximal convoluted tubule. SGLT2 inhibitors like canagliflozin, dapagliflozin, and empagliflozin work by inhibiting glucose reabsorption in the kidney, thereby increasing glucose excretion and lowering blood glucose levels. They provide glycemic control with a low risk of hypoglycemia when used alone but a higher risk when combined with insulin or insulin secretagogues. Side effects include genital infections, urinary
- Insulin therapy is eventually required for many patients with type 2 diabetes as pancreatic function continues to decline over time. Basal insulin therapy is usually initiated first to control fasting blood glucose, with the addition of prandial insulin if A1C levels remain high.
- Guidelines recommend starting basal insulin when A1C is ≥8.5% or if the total daily basal insulin dose nears 1 unit/kg/day. Prandial insulin should be added if the daily basal dose exceeds 0.5 units/kg/day or to control post-meal blood glucose excursions.
- Insulin regimens can include basal-bolus therapy with long or intermediate acting basal insulin plus rapid-acting pr
Intensification Options after basal Insulin RevisitedUsama Ragab
Intensification Options revisited
By Dr. Usama Ragab Youssif
Add an OAD
Add a short-acting insulin at mealtime
Switch to premixed insulins
Novel insulin combinations
Basal insulin/GLP-1 RA combinations
This document provides treatment guidelines for diabetes mellitus. It discusses the types of diabetes, symptoms, complications, goals of treatment, and treatment options. Treatment involves lifestyle changes like diet and exercise. Pharmacological treatment starts with metformin for type 2 diabetes and insulin for type 1 diabetes. Insulin therapy is initiated at 0.4-1.0 units/kg/day for type 1 diabetes. Additional agents may be added if blood sugar levels remain uncontrolled. The goal of treatment is to achieve a hemoglobin A1c level below 7% through lifestyle management and medication adjustments.
1) Insulin therapy is recommended for type 2 diabetes patients with an HbA1c ≥9%, significant hyperglycemia, or when other treatments fail to control blood glucose levels.
2) There are several options for insulin therapy including basal insulin only, premixed insulin, or basal-bolus regimens. Basal insulin aims to provide background insulin levels while bolus insulin covers mealtime spikes.
3) When initiating insulin, it is important to assess the patient's needs, educate them on self-monitoring, and start at a low dose such as 0.1-0.2 units/kg of basal insulin daily to minimize risks of hypoglycemia and weight gain. The dose is then gradually
Type 2 dm gdm new updates & guidelinesSachin Verma
Type 2 diabetes is a multifactorial disorder characterised by progressive pancreatic beta-cell dysfunction and insulin- resistance, leading to relative insulin deficiency, chronic hyperglycaemia, and various complications.
The treatment options for this disorder, which aim at correcting one or other of the two major pathophysiological mechanisms, have been hamstrung by unacceptable side-effects, lack of patient acceptability, and loss of efficacy over time.
Insulin pumps provide patients with type 1 diabetes a method of continuous subcutaneous insulin infusion as an alternative to multiple daily insulin injections. Insulin pumps can help improve glycemic control and reduce hypoglycemic episodes compared to multiple daily injections. The document discusses different insulin types used in pumps, how pumps work, and guidelines for when insulin pump therapy is recommended.
There are different kinds of insulin that
people with diabetes can use every
day to help them stay healthy. This
booklet gives some basic facts about
insulin. Use this booklet to help you
talk to your healthcare provider about
DR. Wedad Bardisi DM Saudi Guideline.pptxFayzaRayes
Diabetes is a serious and growing problem in Saudi Arabia. Studies show prevalence of diabetes in Saudi Arabia is around 23-34%, and costs associated with diabetes and its complications place a significant burden on the healthcare system. The guidelines provide recommendations for screening, diagnosing, and managing diabetes through lifestyle changes and pharmacologic treatment. The guidelines recommend metformin as initial treatment and emphasize individualizing treatment based on patient factors. Glycemic targets of A1C <7% and fasting blood glucose 70-130 mg/dL are provided.
DR. Wedad Bardisi DM Saudi Guideline.pptxFayzaRayes
Diabetes is a serious and growing problem in Saudi Arabia. Studies show prevalence rates of 23-34% and costs of $3,686 more per person with diabetes annually. Guidelines recommend screening those over 40 every 3 years or those at high risk. Treatment begins with lifestyle changes and metformin, adding other oral drugs or insulin as needed to reach an A1C target of 7%. Insulin therapy is often required long-term for type 2 diabetes control. Low-dose aspirin is recommended for cardiovascular protection depending on age and risk factors.
This document summarizes the management and treatment of diabetes. It discusses:
1) The classification of type 1 and type 2 diabetes, their typical presentations, and diagnostic criteria.
2) Guidelines for initial treatment including lifestyle changes and metformin for type 2 diabetes. Adding sulfonylureas or insulin if glycemic goals are not met.
3) Treatment of type 1 diabetes focuses on intensive insulin therapy to control blood glucose and reduce complications.
4) Screening and treatment of complications like nephropathy, retinopathy, and neuropathy are also covered.
Insulin degludec is an ultralong-acting basal insulin analogue administered via once daily subcutaneous injection to help control blood sugar levels in diabetes. It has a duration of action of up to 40 hours, making it suitable as a once-daily treatment. Clinical trials found it to be as effective as insulin glargine at reducing HbA1c levels while having a lower risk of hypoglycemia, especially nocturnal hypoglycemia. Insulin peglispro is an experimental basal insulin consisting of insulin lispro covalently attached to polyethylene glycol. Phase II clinical trials found it reduced blood glucose variability compared to insulin glargine while maintaining similar HbA1c lowering and hypoglycemia rates,
- The patient has type 2 diabetes and stage 3 chronic kidney disease, so metformin was discontinued.
- Liraglutide treatment has been shown to decrease the risk of cardiovascular death but not cause significant weight loss or increase cancer risk.
- Glyburide should be avoided given the patient's low GFR, while linagliptin can be used.
- Most insulins can be used but doses may need adjusting to avoid hypoglycemia risk from prolonged half-lives in kidney disease. Glucagon-like peptide-1 receptor agonists are also options but can increase hypoglycemia risk if used with insulin.
- GLP-1 receptor agonists are recommended as first-line treatment after metformin for type 2 diabetes due to their ability to reduce weight and cardiovascular risk factors like lipids and blood pressure while improving glycemic control with a low risk of hypoglycemia. Early initiation of GLP-1 agonists may help preserve beta-cell function by reducing glucotoxicity and increasing beta-cell mass. Exenatide was the first incretin mimetic and works similarly to natural GLP-1 but is resistant to degradation, allowing twice-daily dosing. Newer long-acting GLP-1 agonists only require once weekly or daily dosing. Nausea is a common side effect but usually mild and intermittent
This document provides an overview and update on treatment strategies for diabetes mellitus type 2 (DM2). It discusses the progressive nature of DM2 and impact of uncontrolled hyperglycemia on microvascular and macrovascular disease. It summarizes the results of major clinical trials on the impact of intensive therapy for diabetes. It also reviews glycemia targets and notes that many patients are not meeting the recommended A1c goal of less than 7%. The document discusses various classes of anti-hyperglycemic medications including their mechanisms of action, efficacy, and side effects. It provides guidance on initiating and adjusting injectable therapies.
Highlights of ADA guidelines 2015 in Diabetes managementAhmed Elmoughazy
This document summarizes guidelines from the American Diabetes Association for the management of diabetes in 2015. It covers classification of diabetes, criteria for testing and diagnosis, targets for glycemic control, recommendations for treatment including lifestyle changes and medications, and management of cardiovascular risk factors and kidney disease complications. The guidelines provide evidence-based standards to guide clinical decision making for diabetes care.
This document provides guidelines for managing diabetes care in the hospital. The goals are to prevent hyperglycemia and hypoglycemia, promote short hospital stays, and ensure effective care transitions. It recommends using computerized order sets for glucose control and ordering an HbA1c test on admission. Target blood glucose levels are outlined for critically ill and non-critically ill patients. Insulin therapy guidelines, treating hypoglycemia, and managing special situations like steroids or enteral feeding are also covered.
Similar to International journal-of-diabetes-and-clinical-research-ijdcr-5-083 (20)
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
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hours.
2) Ultra fast acting: Apidra (Fiasp) Which begins to
act 4-7 minutes before regular apidra and lasts for
around 3 hours.
3) Short acting: Reaches systemic circulation in 30 min,
peaks after about 2-3 hours and remains active for
around 3-6 hours.
4) Intermediately acting: Onset of action after 2-4
hours, peaks 4-12 hours later and remains active for
about 12-18 hours.
5) Long acting: Gradually absorbed from injection site
due to unique preparation. Its activity can range from
18-24 hours. The ultra-long acting insulin degludec,
has plasma concentrations measurable beyond 24
hours allowing for flexible dosing.
The table, summarises various insulin types and pre-
parations available in market (Table 1).
There are many reasons that patients do not achieve
glycaemic targets. These can be patient factors, disease
related factors and also clinical inertia, for example, de-
lay in intensification of treatment [7]. (Table 2)
The Evidence Based Use of Various Insulin Types
and Regimes are Discussed Below:
Basal insulin and dose titration
When initiating insulin in T2DM, NPH insulin is the
preferred option either once or twice daily, according
to the need, unless:
• Individual’s lifestyle is affected by symptomatic hypo-
glycaemia, or
• Twice daily insulin injection is deemed inappropriate
due to other reasons.
In such situations a long-acting insulin analogue, de-
temir or glargine, should be considered [5]. The newer
insulins like degludec, toujeo (high strength insulin) and
biosimilars (example: Abasaglar) can also be used.
It can be initiated as 10 U/day or 0.1-0.2 U/kg/day.
To reach the target fasting plasma glucose (FPG) level,
titration of insulin is done by 10-15% or 2-4 units (U)
once or twice weekly [8].
The duration of action of lantus and NPH is around
24 hours and 14 hours or more respectively. The effecti-
veness of basal insulin is estimated by FPG levels and
titrated accordingly. The best time to dose basal insulin
is either with evening meal or before bedtime [8] (Table
3).
The benefit of long-acting analogue insulins over NPH
insulin, appears to be in the lower incidence of noctur-
nal hypoglycaemia, which must be a consideration when
determining insulin choice. Due to its lesser day-to-day
variability, degludec has the potential to further reduce
the risk of hypoglycaemia than other long-acting basal
insulins [9]. The DEVOTE study showed that degludec
was non-inferior to glargine with respect to incidence
of cardiovascular events with significant reductions in
severe hypoglycaemia, especially nocturnal [10].
High-strength insulin products such as insulin glargi-
ne 300 units/ml (Toujeo) have been developed for peo-
ple with type 1 or type 2 diabetes who have large daily
insulin requirements to reduce the number and volume
of injections. In 3 randomised controlled trials (RCTs) in
2496 adults with type 2 diabetes, Toujeo had similar ef-
ficacy to insulin glargine 100 units/ml (Lantus) in terms
of HbA1c reduction [11].
Toujeo is not bioequivalent to insulin glargine 100
units/ml (Lantus) and dose adjustment is needed when
patients are switched from Lantus or other basal insu-
lins to Toujeo or vice versa.
Premixed insulin and dose titration
Premixed insulin therapy is suitable for patients who
cannot count carbohydrates or those who have consistent
Table 2: The causes of secondary drug failure to Oral hypoglycemic agents [31].
The patient factors Disease related factors
• An improper diet
• Obesity
• Lack of exercise
• Lack of knowledge of diabetes and stress
• An impaired C-peptide response to a meal
• An enhanced basal rate of hepatic glucose production which is
insufficiently suppressed by insulin
• Impaired storage of glucose as glycogen
Table 1: Various insulin types and preparations available in
market.
Description Insulin and insulin analogue
preparation
Rapid acting insulin Lispro
Aspart
Glulisine
Short acting insulin Regular/soluble insulin
Ultra-fast acting insulin Aspart (Fiasp)
Intermediate acting insulin NPH or Isophane insulin
Long acting insulin Glargine
Detemir
Degludec (Ultra-long acting)
Toujeo (Glargine-high strength
insulin)
Biosimilar insulin Abasaglar (Glargine)
Premixed insulin (Human) 70% NPH 30% Regular
50% NPH 50% Regular
Premixed insulin
(Analogues)
75% NPL 25% Lispro
50% NLP 50% Lispro
70% Protamine aspart 30% Aspart
NPL: Neutral Protamine Lispro; NPH: Neutral Protamine
Hagedorn.
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• 0.2 U/kg/day for Hba1c < 9% and 0.4 U/kg/day for
Hba1c > 9%. Patients with Hba1c > 9% are at incre-
ased risk of complications, hence optimal glycaemic
control is required.
• Twice a day premixed insulin if total daily dose of insu-
lin (TDD) is more than 20 U, dosed along with breakfast
and evening meal based upon carbohydrate content in
meal and daily activity.
• The 50:50 ratio can be considered for premix analo-
gues, if a single dose exceeds 30 U.
Tanaka and Ishii [16] found lispro mix 50/50 insulin,
which is high proportion insulin containing 50% rapid and
50%intermediateactinginsulin,controlledthepost-pran-
dial glucose (PPG) and stabilised the diurnal blood gluco-
se variations in patients who had poor control on insulin
70/30 or 75/25. Lispro 50/50 had more rapid onset of
action with lower risk of nocturnal hypoglycaemia.
The initial dose can be titrated once or twice weekly
for 12 weeks and every two weeks thereafter, according
to the FPG targets as per algorithm below [15] (Table 4).
eating patterns and routine lifestyle. Initiating insulin the-
rapy with premixed insulin once daily, opens the possibili-
ty of a stepwise approach to intensify therapy to twice or
thrice daily to achieve target HbA1c levels [12]. NICE [5]
recommends to start premixed insulin if HbA1c > 9.0%.
A twice daily dose has been recommended for initia-
tion of premix insulin but a once daily dose has been found
to be effective for patients who are reluctant to start insu-
lin and require < 20 units/day [13]. Kilo, et al. [14] evalua-
ted the effectiveness of initiating patients on a simple once
daily regimen with insulin aspart 30/70, NPH insulin and
biphasic human insulin 30/70, in combination with metfor-
min. The results showed a 1.1%-1.3% reduction of Hba1c
for all groups with FPG reductions of 31% for aspart 30/70,
37% for NPH and 28% for biphasic human insulin, conclu-
ding that each one could safely be added to metformin.
Premixed insulin can be initiated according to the
following common standards [15]:
• 10 U/day once daily either in the morning or evening
or 0.3-0.5 U/kg/day, depending on glucose level.
Table 3: Evidence of analogue insulin used in the treatment of T2DM.
Study Intervention Outcomes Statistical significance
Swinnen, et al. [32]
(24 week
randomised trial)
Once daily glargine
versus twice daily
detemir
27.5% glargine and 25.6% detemir achieved HbA1c < 7% P = 0.254
Greater proportion detemir patients < 6.5% Weight gain
higher for glargine
P = 0.017
Lower doses of glargine for equivalent glycaemic control P < 0.001
Hypoglycaemia similar P < 0.001
Meneghini, et al.
[33]
(26 week
randomised trial)
Detemir versus
glargine
38% detemir and 53% glargine achieved HbA1c < 7%
Weight loss with detemir (- 0.49 kg) versus weight gain
with glargine (+ 1.0)
P = 0.026
Lower doses of glargine for equivalent glycaemic control P = 0.0208
Reduced incidence of hypoglycaemia for detemir P = 0.034
Waugh, et al. [34].
Systematic review
of long-acting insulin
analogues
Glargine versus
NPH
Similar improvements to HbA1c
Hypoglycaemia, symptomatic, nocturnal and severe
Not Significant (NS)
Mixed results some
significant reduction for
glargine,
some NS
Weight gain for both glargine and NPH NS
Mixed results
Detemir versus
NPH
Similar improvements in HbA1c P < 0.05
Symptomatic and severe hypoglycaemia P < 0.00001 [34]
Less nocturnal hypoglycaemia for detemir
Less weight gain for detemir than NPH
P < 0.05
Zinman, et al. [35]
(1 year trial)
Degludec versus
glargine
Reduction in HbA1c similar in both groups
Insulin doses similar
Confirmed hypoglycaemia similar
P = 0.40
Confirmed nocturnal hypoglycaemia less for degludec P = 0.106
Less severe hypoglycaemia for degludec P = 0.004
Similar weight gain in both groups P = 1.017
Marso SP, et al. [10]
(DEVOTE, 3 Year
trial)
Degludec versus
Glargine
(Cardiovascular
safety)
Primary outcome
Severe hypoglycaemia incidence
Hazard ratio 0.91, 95% CI
0.78-1.06
P < 0.001 for non-inferiority
Rate ratio 0.6, P < 0.001
for superiority
Odds ratio 0.73, P < 0.001
for superiority
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Basal-bolus regimen and dose titration
Basal-bolus regimen is an intensified insulin therapy
when target glycaemic control is not achieved with ba-
sal insulin. This regimen mimics the physiological insulin
secretion from the pancreas. The intermediate or long
acting insulin is given as basal insulin. The rapid or short-
acting insulin is given as bolus insulin before meal. This
regimen needs frequent and active self-monitoring,
knowledge on insulin-carbohydrate ratio and correction
factors (CF), and titration of insulin dose to achieve tar-
get glycaemic control [20].
The basal-bolus insulin regimen can be initiated by
intensifying the basal or basal plus regimen. To initiate,
the TDD (0.6-1.0 units/kg) is first calculated. Then 50%
of TTD is given as basal insulin which is administered at
bedtime. The remaining 50% is divided between bolus
doses for breakfast, lunch and dinner [21].
There are different methods of dose titration, adju-
sting 2-3 units in appropriate dose every 3-7 days to
achieve the target. Generally, titration of basal insulin is
based on FPG, while bolus insulin is based on pre pran-
dial or PPG levels at mentioned in table 6 [21].
• Increase or decrease insulin by 10% depending on blo-
od glucose reading shown in Table 6 [21].
Basal-plus insulin
The addition of a single prandial insulin injection to
the already existing basal regimen before the main meal
or the meal consistent with highest PPG, is referred to
as a “basal-plus” strategy [17,18]. This has been an ef-
fective method when intensifying insulin therapy, befo-
re a full basal-bolus regimen is to be implemented [19].
Careful patient evaluation and timing are necessary due
to the complex nature of this regimen and the need for
multiple daily injections and multiple daily glucose moni-
toring. Therefore younger, highly motivated, active indi-
viduals with variable eating habits with both type 1 and
T2DM will be best suited for such a regimen (Table 5).
From the results obtained in table, not all differences
observed were statistically significant when comparing
them in the use of this strategy to basal-bolus and pre-
mixed regimens.
Table 5: Evidence for the use of the basal-plus strategy.
Trial Duration & Population Size Intervention Target HbA1c Results
1.2.3 study [36] 24 weeks
115 subjects
vs.
113 subjects
Insulin glargine + OHA’s + once
daily insulin glulisine
vs.
insulin glargine + OHA’s + twice
daily insulin glulisine
< 7% • Proportion achieving
target HbA1c: 30% vs.
33%
• Severe hypoglycaemia
0.28 vs. 0.89 events/
patient year
• Weight change + 3.8
vs. + 4.1 kg
Stepwise [18] 48 weeks
150 subjects
vs.
146 subjects
Insulin detemir + OHA’s + stepwise
aspart to largest meal (based on
premeal glucose): Simple STEP
vs.
Insulin detemir + OHA’s + stepwise
aspart to largest meal (based on
post-meal glucose)
Extra STEP
< 7% • Proportion achieving
target HbA1c: 31% vs.
27%
• Severe hypoglycaemia
0.04 vs. 0.01 events/
patient year
• Weight change + 2.7
vs. + 2.0 kg
All to target [37] 60 weeks
192 subjects
vs.
189 subjects
vs.
191 subjects
Twice daily premixed insulin + 2-3
OHA’s
vs.
insulin glargine + once daily
glulisine + 2-3 OHA’s
vs.
insulin glargine + stepwise addition
of insulin glulisine + 2-3 OHA’s
< 7% • Proportion achieving
target HbA1c: 39% vs.
49% vs. 45%
• Severe hypoglycaemia
0.02 vs. 0.1 vs. 0.2
events/patient year
Table 6: Insulin dose optimisation according to blood glucose readings.
Basal/bolus insulin Time of self-monitoring blood glucose
Basal insulin Fasting pre-breakfast blood glucose
Pre-breakfast bolus insulin 2-hours post-breakfast or pre-lunch blood glucose
Pre-lunch bolus insulin 2-hours post-lunch or pre-dinner blood glucose
Pre-dinner bolus insulin post-dinner or bedtime blood glucose
Table 4: Premixed insulin dose titration.
Pre-meal plasma glucose level Dose titration units (U)
≤ 100 mg/dl (≤ 5.6 mmol/l) - 2U
100-110 mg/dl (5.7-6.1 mmol/l) No change
110-140 mg/dl (6.2-7.8 mmol/l) + 2U
140-180 mg/dl (7.9-10 mmol/l) + 4U
≥ 180 mg/dl (≥ 10 mmol/l) + 6U
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formulations, they have a more predictable onset and
duration of action, along with increased flexibility for
dose administration and meal times [25].
A comparative analysis of various studies comparing
premix human insulin vs. premix insulin analogues is gi-
ven in the Table 8.
In conclusion, premix analogues are similar to hu-
man insulin but some trials have shown better HbA1c
reduction. The main advantage is better post-prandial
glucose control and less delayed hypoglycaemia.
Premixed versus basal insulin
When initiating insulin, the HCP could consider pre-
mixed or basal insulin, depending on clinical situation
(Table 9).
These studies show that glycaemic control can be
better with pre-mixed rather than basal insulin, but with
higher risk of hypoglycaemic episodes and weight gain.
Fasting glucose levels contribute to HbA1c at all levels
of glycaemia, but when HbA1c is less than 9%, prandial
glucose levels become more important. However, further
analysis of DURABLE trial showed that only premixed li-
spro insulin decreased prandial glucose. Where initial
HbA1c was less than 9%, there is greater improvement
in HbA1c with pre-mixed insulin rather than basal [26].
Thus for the following patients, pre-mixed insulin
may provide better glycaemic control [27]:
• HbA1C > 8.5%.
• Poor patient compliance with high demands of basal
bolus regimen.
• To titrate the bolus dose, add or deduct the cor-
rection dose to or from the bolus dose.
Correction dose = Excess or deficit blood glucose × CF.
CF = 1500/TDD (will give the value in mg/dl, used
when patient is on rapidly acting insulin)
• To titrate the basal dose, some use Treat-to-Target
Trial’s titration schedule as per table [22] (Table 7).
Giugliano, et al. [23] concluded it to be the best regi-
men to attain the target glycaemic control. The patients
treated with basal-bolus regimen had statistically signi-
ficant achievement of HbA1c target of < 7% compared
to biphasic insulin, 63.5% vs. 50.8% (odd ratio 0.57 [95%
CI 0.36-0.90]) (p = 0.034). No difference was seen in ter-
ms of incidence of hypoglycaemia or weight gain betwe-
en the two regimens.
In Treating to Target in Type 2 Diabetes (4-T) study,
67.7% of the patients in biphasic group, 73.6% in the
prandial group and 81.6% in the basal group were la-
ter intensified to basal-bolus regimen, and two-third of
them reached the glycaemic target [24].
Premix human insulin vs. Premix analogue insulin
Insulin analogues closely mimic physiological endo-
genous insulin secretion. Compared to human insulin
Table 8: Comparing premix human insulin vs. premix insulin analogues.
Glycaemic control
Name of study Study
population
size (n)
Patients
included
Drugs compared Inference p Value
Matto, et al. [38] n = 151 Type 2
diabetes
Insulin lispro 75/25
vs.
Human insulin 70/30
Reduction in mean 4 point blood
glucose profile:
Insulin lispro > Human insulin
p = 0.004
Malone, et al. [39] n = 84 Type 2
diabetes
Insulin lispro 75/25
vs.
Human insulin 70/30
PP blood glucose excursion:
Lower with insulin lispro than
human insulin
p < 0.001
AUC in glucose concentration -
time curve: Less in insulin lispro
than human insulin
----
Christiansen, et al.
[40]
n = 403 Type 2
diabetes
BI Asp 30
vs.
NPH (BD)
Comparable reduction in HbA1c
with both
(0.67% with BI Asp 30
0.61% with NPH)
----
PP increment over 3 meals:
Lower with BI Asp 30 than NPH
p < 0.0001
Boehm, et al. [41] n = 294 Type 1
diabetes
and
Type 2
diabetes
BI Asp 70/30
vs.
Human insulin 70/30
Reduction in HbA1c:
Similar with both
----
PP blood glucose control:
BI Asp > Human Insulin
----
PP: Post Prandial; AUC: Area Under Curve; BI Asp: Biphasic Insulin Aspart.
Table 7: Treat-to-Target trial’s titration schedule for basal insulin.
Fasting blood glucose To increase in basal insulin
120-140 mg/dl (6.7-7.8 mmol/l) 2 units
141-160 mg/dl (7.9-8.9 mmol/l) 4 units
161-180 mg/dl (9.0-10 mmol/l) 6 units
> 180 mg/dl (> 10 mmol/l) 8 units
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comparability studies that demonstrate similarity to the
reference medicine. Biosimilars have the potential to
offer considerable cost savings [28].
Insulin glargine biosimilar (Abasaglar) is licensed for
the treatment of diabetes mellitus both type 1 and type
2. Abasaglar is a basal insulin for once daily use and is bio-
equivalent to insulin glargine (Lantus). Abasaglar is avai-
lable as cartridges of 100 units/ml for use in the reusable
pen or as a pre filled Abasaglar pen 100 units/ml [28].
The efficacy and safety of Abasaglar is non-inferior
to Lantus and this evidence is based on the 2 phase III
studies of insulin glargine biosimilar (Abasaglar) in peo-
ple with type 1 and type 2 diabetes, ELEMENT 1 [29] and
ELEMENT 2 [30], respectively.
• Low (< 150 mg/dl) fasting or pre-prandial glucose but
high HbA1c.
Therefore, despite ADA [8] advising to start patien-
ts on basal insulin, there may be situations where pre-
mixed insulin maybe more suitable.
Biosimilar insulin
A biosimilar medicine is a biological medicine that is
developed to be very closely similar to an existing bio-
logical medicine (the reference medicine). The active
substance of both is essentially the same biological sub-
stance but, just like the reference medicine, the biosimi-
lar has some element of natural variability. Biosimilars
undergo a regulatory process which demands extensive
Table 9: Comparing pre-mixed and basal insulin initiation regimens in T2DM.
Study Population criteria Types of insulin used Effect on HbA1c Adverse effects
Giugliano, et al. [23]
Meta-analysis of 16
RCTs
7759 patients with
T2DM where RCTs
were for at least 12
weeks
Biphasic premixed
insulins, short-acting
prandial insulins and
basal insulin
Premixed insulin lead to
OR 1.88 to achieve HbA1c
< 7% compared with basal
insulin
Premixed insulin was
associated with 0.34 more
hypoglycaemic events/
patient/30 days than basal
insulin
1 kg more weight gain was
seen with premixed insulins
Janka, et al. [42]
Multinational,
multicentre, open
parallel group study
371 insulin naïve
individuals with T2DM
and HbA1c between
7.5-10%
Once daily morning
insulin glargine and
OHAs compared with
30% regular/70% human
NPH insulin twice daily
alone
Reduction of 1.64%
with glargine compared
to reduction of 1.31%
premixed insulin (p =
0.0003)
Glargine led to 45.5%
of patients with HbA1c
≤ 7.0% compared to
28.6% without confirmed
nocturnal hypoglycaemia
(p = 0.0013)
4.07 hypoglycaemic events/
patient year with glargine
9.87 hypoglycaemic events/
patient year with premixed
insulin
(p < 0.0001)
Initiate study [43] 28
week parallel-group
study
233 insulin naïve
patients with HbA1c ≥
8.0% on OHAs
Metformin was titrated
to 2550 mg/day
before insulin initiation
Premixed 70/30% twice
daily insulin compared
with glargine at bedtime
Mean HbA1c was 6.91%
with premixed versus
7.41% with basal insulin (p
< 0.01)
HbA1c reduced by 2.79%
with premixed compared
to 2.36% reduction with
basal insulin (p < 0.01)
especially if HbA1c was >
8.5%
HbA1c target of ≤ 6.5%
was achieved in 14% more
patients with pre-mixed (p
< 0.05)
2.7 more hypoglycaemic
episodes/year seen with
premixed versus basal
insulin (p < 0.05)
1.9 kg more weight gain
with premixed versus basal
insulin (p < 0.01)
Durable trial [44]
24 week randomised,
multicentre,
multinational, open
parallel trial
2091 insulin naïve
adults patients with
T2DM with HbA1c
> 7% on at least 2
OHAs for 90 days
Twice daily premixed
lispro protamine
suspension 75% and
25% lispro or daily
glargine with continuation
of OHAs in both groups
7.2% people achieved
HbA1c target < 7% with
premixed (p < 0.001)
Premixed insulin showed
1.8% reduction compared
to 1.7% seen with glargine
(p = 0.005)
1.1 kg more weight gain
seen with premixed rather
than basal insulin (p <
0.0001)
4.9 more hypoglycaemic
episodes/patient/year with
premixed compared to
basal insulin (p = 0.007)
but fewer nocturnal
hypoglycaemia (p = 0.007)
7. ISSN: 2377-3634
DOI: 10.23937/2377-3634/1410083
Ali et al. Int J Diabetes Clin Res 2018, 5:083 • Page 7 of 8 •
12. Unnikrishnan AG, Tibaldi J, Hadley-Brown M, Krentz AJ, Li-
gthelm R, et al. (2009) Practical guidance on intensification
of insulin therapy with BIAsp 30: A consensus statement.
Int J Clin Prac 63: 1571-1577.
13. Vaag A, Lund S (2011) Therapy of Endocrine Disease:
Insulin initiation in patients with type 2 diabetes mellitus:
Treatment guidelines, clinical evidence and patterns of use
of basal vs premixed insulin analogues. Eur J Endocrinol
166: 159-170.
14. Kilo C, Mezitis N, Jain R, Mersey J, McGill J, et al. (2003)
Starting patients with type 2 diabetes on insulin therapy
using once-daily injections of biphasic insulin aspart 70/30,
biphasic human insulin 70/30, or NPH insulin in combina-
tion with metformin. J Diabetes Complications 17: 307-313.
15. Indian Consensus Group (2009) Premix insulin: Initiation
and continuation guidelines for management of diabetes in
primary care. JAPI 57: 42-46.
16. Tanaka M, Ishii H (2010) Pre-mixed rapid-acting insulin
50/50 analogue twice daily is useful not only for controlling
post-prandial blood glucose, but also for stabilizing the diur-
nal variation of blood glucose levels: switching from pre-
mixed insulin 70/30 or 75/25 to pre-mixed insulin 50/50. J
Int Med Res 38: 674-680.
17. Lankisch MR, Ferlinz KC, Leahy JL, Scherbaum WA, Orals
Plus Apidra and LANTUS (OPAL) Study Group (2008) In-
troducing a simplified approach to insulin therapy in type
2 diabetes: A comparison of two single-dose regimens of
insulin glulisine plus insulin glargine and oral anti-diabetic
drugs. Diabetes Obes Metab 10: 1178-1185.
18. Meneghini L, Mersebach H, Kumar S, Svendsen AL, Her-
mansen K, et al. (2011) Comparison of 2 intensification re-
gimens with rapid-acting insulin aspart in type 2 diabetes
mellitus inadequately controlled by once-daily insulin dete-
mir and oral antidiabetes drugs: The step-wise randomized
study. Endocr Pract 17: 727-736.
19. Barnett A, Begg A, Dyson P, Feher M, Hamilton S, et al.
(2008) Insulin for type 2 diabetes: Choosing a second-line
insulin regimen. Int J Clin Pract 62: 1647-1653.
20. Frits H (2014) Insulin Regimens. DIAPEDIA.
21. Petznick A (2011) Insulin management of type 2 diabetes
mellitus. Am Fam Physician 84: 183-190.
22. Riddle MC, Rosenstock J, Gerich J, Insulin glargine 4002
study investigators (2003) The treat-to-target trial: Rando-
mized addition of glargine or human NPH insulin to oral the-
rapy of type 2 diabetic patients. Diabetes Care 26: 3080-
3086.
23. Giugliano D, Maiorino MI, Bellastella G, Chiodini P, Ceriello
A, et al. (2011) Efficacy of insulin analogs in achieving the
Hemoglobin A1c target of <7% in type 2 diabetes: Meta-a-
nalysis of randomized controlled trials. Diabetes Care 34:
510-517.
24. Holman RR, Farmer AJ, Davies MJ, Levy JC, Darbyshire
JL, et al. (2009) Three-year efficacy of complex insulin re-
gimens in type 2 diabetes. N Engl J Med 361: 1736-1747.
25. Garber AJ, Ligthelm R, Christiansen JS, Liebl A (2007) Pre-
mixed insulin treatment for type 2 diabetes: Analogue or
human? Diabetes Obes Metab 9: 630-639.
26. Scheen AJ, Schmitt H, Jiang HH, Ivanyi T (2015) Individua-
lizing treatment of type 2 diabetes by targeting postpran-
dial or fasting hyperglycaemia: Response to a basal vs a
premixed insulin regimen by HbA1c quartiles and ethnicity.
Diabetes Metab 41: 216-222.
Conclusion
HCPs should individualise the treatment and discuss
with patients, regarding various options and educate them
on insulin therapy. Basal insulin is preferred as an augmen-
tation therapy when adding on to the oral hypoglycaemic
agents. Replacement therapy includes basal-bolus regi-
men with correction dose or consider premixed insulin if
appropriate [21].
Glucose control, adverse effects, cost, adherence
and quality of life should be considered while choosing
therapy. Titration of insulin over time is critical for glyca-
emic control and to prevent diabetes related complica-
tions [21]. Though basal-bolus resembles physiological
insulin secretion, premixed analogues are good option
with less demanding glucose monitoring and injection
schedule. The rule should be tailoring the insulin treat-
ment to suit patient and not the other way around [27].
Acknowledgment
Amit dey, Gloria Nomusa Cele, Karen Blackwood,
Meela Ali, Naved Akhtar, Oye Akindele and Swati Dho-
lakia.
References
1. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, et
al. (2000) Association of glycaemia with macrovascular and
microvascular complications of type 2 diabetes (UKPDS
35): Prospective observational study. BMJ 321: 405-412.
2. International Diabetes Federation (2012) Global guideline
for type 2 diabetes.
3. Kramer CK, Zinman B, Retnakaran R (2013) Short-term
intensive insulin therapy in type 2 diabetes mellitus: A sy-
stematic review and meta-analysis. Lancet Diabetes Endo-
crinol 1: 28-34.
4. NHS (2013) Greater glasgow and clyde: Guidelines for in-
sulin initiation and adjustment in primary care in patients
with type 2 diabetes: For the guidance of diabetes specialist
nurses.
5. NICE (2017) Type 2 diabetes in adults: Management. NICE
guideline [NG28].
6. MHRA (2011) Insulin combined with pioglitazone: Risk of
cardiac failure.
7. Khunti K, Wolden ML, Thorsted BL, Andersen M, Davies
MJ (2013) Clinical inertia in people with type 2 diabetes.
Diabetes Care 36: 3411-3417.
8. ADA (2017) Standards of medical care in Diabetes-2017.
Diabetes Care 40: S1-S135.
9. Heise T, Tack CJ, Cuddihy R, Davidson J, Gouet D, et al.
(2011) A new-generation ultra-long-acting basal insulin with
a bolus boost compared with insulin glargine in insulin-nai-
ve people with type 2 diabetes: A randomized, controlled
trial. Diabetes Care 34: 669-674.
10. Marso SP, McGuire DK, Zinman B, Poulter NR, Emerson
SS, et al. (2016) Efficacy and safety of degludec versus
glargine in type 2 diabetes. N Engl J Med 377: 723-732.
11. NICE (2015) Type 2 diabetes in adults: High strength in-
sulin glargine 300 units/ml (toujeo). Evidence summary
[ESNM 65].
8. ISSN: 2377-3634
DOI: 10.23937/2377-3634/1410083
Ali et al. Int J Diabetes Clin Res 2018, 5:083 • Page 8 of 8 •
36. Davidson MB, Raskin P, Tanenberg RJ, Vlajnic A, Hollan-
der P (2011) A stepwise approach to insulin therapy in pa-
tients with type 2 diabetes mellitus and basal insulin treat-
ment failure. Endocr Pract 17: 395-403.
37. Riddle MC, Rosenstock J, Vlajnic A, Gao L (2014) Ran-
domized, 1-year comparison of three ways to initiate and
advance insulin for type 2 diabetes: Twice-daily premixed
insulin versus basal insulin with either basal-plus one pran-
dial insulin or basal-bolus up to three prandial injections.
Diabetes Obes Metab 6: 396-402.
38. Mattoo V, Milicevic Z, Malone JK, Schwarzenhofer M, Ekan-
gaki A, et al. (2003) A comparison of insulin lispro Mix25
and human insulin 30/70 in the treatment of type 2 diabetes
during ramadan. Diabetes Res Clin Pract 59: 137-143.
39. Malone JK, Woodworth JR, Arora V, Yang H, Campaigne
BN, et al. (2000) Improved postprandial glycemic control
with Humalog? Mix75/25 after a standard test meal in pa-
tients with type 2 diabetes mellitus. Clin Ther 22: 222-230.
40. Christiansen JS, Vaz JA, Metelko Z, Bogoev M, Dedov I
(2003) Twice daily biphasic insulin aspart improves po-
stprandial glycaemic control more effectively than twice
daily NPH insulin, with low risk of hypoglycaemia, in patien-
ts with type 2 diabetes. Diabetes Obes Metab 5: 446-454.
41. Boehm BO, Home PD, Behrend C, Kamp NM, Lindholm
A (2002) Premixed insulin aspart 30 vs. premixed human
insulin 30/70 twice daily: A randomized trial in Type 1 and
Type 2 diabetic patients. Diabet Med 19: 393-399.
42. Janka HU, Plewe G, Riddle MC, Kliebe-Frisch C, Schweitzer
MA, et al. (2005) Comparison of basal insulin added to oral
agents versus twice-daily premixed insulin as initial insulin the-
rapy for type 2 diabetes. Diabetes Care 28: 254-259.
43. Raskin P, Allen E, Hollander P, Lewin A, Gabbay RA, et
al. (2005) Initiating insulin therapy in type 2 diabetes: A
comparison of biphasic and basal insulin analogs. Diabetes
Care 28: 260-265.
44. Buse JB, Wolffenbuttel BH, Herman WH, Shemonsky NK,
Jiang HH, et al. (2009) DURAbility of basal versus lispro
mix 75/25 insulin efficacy (durable) trial 24-week results:
Safety and efficacy of insulin lispro mix 75/25 versus insulin
glargine added to oral antihyperglycemic drugs in patients
with type 2 diabetes. Diabetes Care 32: 1007-1013.
27. Mosenzon O, Raz I (2013) Intensification of insulin therapy
for type 2 diabetic patients in primary care: Basal-bolus
regimen versus premix insulin analogues: When and for
whom? Diabetes Care 36: S212-S218.
28. NICE (2015) Diabetes mellitus type 1 and type 2: Insulin glar-
gine biosimilar (Abasaglar). Evidence summary [ESNM 64].
29. Blevins TC, Dahl D, Rosenstock J, Ilag LL, Huster WJ, et
al. (2015) Efficacy and safety of LY2963016 insulin glargi-
ne compared with insulin glargine (Lantus®
) in patients with
type 1 diabetes in a randomised controlled trial: The ELE-
MENT 1 study. Diabetes Obes Metab 17: 726-733.
30. Rosenstock J, Hollander P, Bhargava A, Ilag LL, Pollom
RK, et al. (2015) Similar efficacy and safety of LY2963016
insulin glargine and insulin glargine (Lantus®
) in patients
with type 2 diabetes who were insulin naïve or previously
treated with insulin glargine: A randomised double blind
controlled trial (the ELEMENT 2 study). Diabetes Obes Me-
tab 17: 734-741.
31. Batra CM (1991) Secondary failure to OHA: Etiology and
management possibilities. Intl J Diab Dev Countries 11: 19-
20.
32. Swinnen SG, Dain MP, Aronson R, Davies M, Gerstein
HC, et al. (2010) A 24-week, randomized, treat-to-target
trial comparing initiation of insulin glargine once-daily with
insulin detemir twice-daily in patients with type 2 diabetes
inadequately controlled on oral glucose-lowering drugs.
Diabetes Care 33: 1176-1178.
33. Meneghini L, Kesavadev J, Demissie M, Nazeri A, Hollan-
der P (2013) Once-daily initiation of basal insulin as add-on
to metformin: a 26-week, randomized, treat-to-target trial
comparing insulin detemir with insulin glargine in patients
with type 2 diabetes. Diabetes Obes Metab 15: 729-736.
34. Waugh N, Cummins E, Royle P, Clar C, Marien M, et al.
(2010) Newer agents for blood glucose control in type 2 dia-
betes: Systematic review and economic evaluation. Health
Technol Assess 14: 1-248.
35. Zinman B, Philis-Tsimikas A, Cariou B, Handelsman Y,
Rodbard HW, et al. (2012) Insulin degludec versus insu-
lin glargine in insulin-naive patients with type 2 diabetes:
A 1-year, randomized, treat-to-target trial (BEGIN Once
Long). Diabetes Care 35: 2464-2471.