This document discusses various types of basal insulin, including their history, mechanisms of action, and clinical benefits. It describes early insulins derived from animals that had issues with impurity and antigenicity. It then covers human insulins like NPH insulin and the development of insulin glargine and insulin detemir as basal insulins that more closely mimic the body's natural basal insulin secretion. Insulin degludec is also introduced as a new basal insulin with an ultra-long duration of action of up to 42 hours and flexible dosing intervals. Clinical trials demonstrate the efficacy of basal insulins like glargine, detemir, and degludec in improving glycemic control and reducing
The document summarizes insulin therapy for diabetes mellitus. It describes the cells in the pancreas that secrete insulin and other hormones. It details the discovery and purification of insulin in the 1920s which revolutionized treatment of diabetes. The document discusses different insulin formulations including short-acting and long-acting types. It explains factors that affect insulin absorption and common dosing regimens for insulin therapy.
Many have troubles choosing the proper insulin type and dosing for their patients.. Here is a quick presentation that introduce you to different studies in that matter.
This presentation is intended for healthcare prfessionals
- The document discusses the use of incretin-based therapies like DPP-4 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes who are not achieving adequate glycemic control on oral medications alone.
- It presents guidelines that recommend starting with basal insulin for patients still above HbA1c targets on dual or triple oral therapy, and then considering adding mealtime insulin, GLP-1 RA, or continuing uptitration of basal insulin if still above targets.
- The case examples show patients started on basal insulin with good initial response but still above goal, so the document discusses options of further uptitrating basal, adding mealtime insulin, or switching to a GLP-1
Diabetes and various types have been discussed in detail as regard for Pg entrance and with various images, tables .....
Topics discussed: 1) introduction
2) types of diabetes
3) comp0lication of diabetes
4) DKA
5) NKHOC
6) Diabetic nephropathy
7) skin diseases in diabetes
This document summarizes a clinical presentation on the basal insulin degludec and barriers to achieving optimal glycemic control. It discusses that hypoglycemia and glucose variability are barriers, and that current basal insulins have limitations like needing to be dosed at the same time daily and intra-patient variability. Insulin degludec was developed to address these barriers with properties like an ultra-long half-life of over 25 hours, very low day-to-day variability in glucose-lowering effect, and the ability to reach steady-state in 3 days. Large clinical trials showed degludec was as effective as glargine at reducing A1c and had a similar or lower risk of hyp
Insulin Initiation : When We should Start with Basal Insulin?mataharitimoer MT
Insulin Initiation : When We should Start with Basal Insulin?
Dr. Agus Taolin , SpPD, FINASIM | PAPDI CABANG BOGOR
Disampaikan pada acara PIT VI IDI Kota Bogor | 9 Nopember 2013
The document summarizes insulin therapy for diabetes mellitus. It describes the cells in the pancreas that secrete insulin and other hormones. It details the discovery and purification of insulin in the 1920s which revolutionized treatment of diabetes. The document discusses different insulin formulations including short-acting and long-acting types. It explains factors that affect insulin absorption and common dosing regimens for insulin therapy.
Many have troubles choosing the proper insulin type and dosing for their patients.. Here is a quick presentation that introduce you to different studies in that matter.
This presentation is intended for healthcare prfessionals
- The document discusses the use of incretin-based therapies like DPP-4 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes who are not achieving adequate glycemic control on oral medications alone.
- It presents guidelines that recommend starting with basal insulin for patients still above HbA1c targets on dual or triple oral therapy, and then considering adding mealtime insulin, GLP-1 RA, or continuing uptitration of basal insulin if still above targets.
- The case examples show patients started on basal insulin with good initial response but still above goal, so the document discusses options of further uptitrating basal, adding mealtime insulin, or switching to a GLP-1
Diabetes and various types have been discussed in detail as regard for Pg entrance and with various images, tables .....
Topics discussed: 1) introduction
2) types of diabetes
3) comp0lication of diabetes
4) DKA
5) NKHOC
6) Diabetic nephropathy
7) skin diseases in diabetes
This document summarizes a clinical presentation on the basal insulin degludec and barriers to achieving optimal glycemic control. It discusses that hypoglycemia and glucose variability are barriers, and that current basal insulins have limitations like needing to be dosed at the same time daily and intra-patient variability. Insulin degludec was developed to address these barriers with properties like an ultra-long half-life of over 25 hours, very low day-to-day variability in glucose-lowering effect, and the ability to reach steady-state in 3 days. Large clinical trials showed degludec was as effective as glargine at reducing A1c and had a similar or lower risk of hyp
Insulin Initiation : When We should Start with Basal Insulin?mataharitimoer MT
Insulin Initiation : When We should Start with Basal Insulin?
Dr. Agus Taolin , SpPD, FINASIM | PAPDI CABANG BOGOR
Disampaikan pada acara PIT VI IDI Kota Bogor | 9 Nopember 2013
1) This document discusses the initiation and adjustment of insulin therapy for type 2 diabetes. It recommends starting with a long-acting basal insulin at bedtime and titrating the dose up gradually until fasting blood glucose is at target levels.
2) If HbA1c remains above 7% after 2-3 months, short-acting insulins should be added at mealtimes starting with breakfast. The doses are then titrated based on pre-meal blood glucose readings.
3) If HbA1c is still not at target after a further 2-3 months, a third daily insulin injection may be needed and post-meal blood glucose should be checked to guide adjustments. The goal is to approximate normal pancreatic
Imeglimin is a novel anti-diabetic drug that targets mitochondrial dysfunction, a key pathological basis for diabetes. It acts on the pancreas to preserve insulin secretion and on tissues to enhance insulin action. Imeglimin has shown efficacy in reducing HbA1c and fasting glucose when used alone or in combination with other drugs. It offers advantages over existing treatments by improving mitochondrial function without inhibiting respiration and has shown protective effects on organs like the kidney and heart. The risk of lactic acidosis may be lower compared to metformin due to distinct mechanisms of action.
The document summarizes the history and types of insulin. It describes the key discoveries in insulin's development, including the identification of the islets of Langerhans in 1869, the discovery that removing the pancreas causes diabetes in 1889, and the isolation of insulin from the pancreas by Banting and Best in 1922. It also discusses the different types of human and analog insulins, including rapid-acting, long-acting, premixed, and biosimilar insulins. The document emphasizes that insulin comes in various preparations that can be tailored to individual patient needs.
Cardiovascular safety of anti-diabetic drugs.Cardiovascular Outcome Trials ...magdy elmasry
Cardiologists and diabetes.Target organs and action mechanism of antidiabetic drugs.Cardiovascular Outcome Trials
( CVOTs ) in Diabetes.Completed and ongoing CVOTs in type 2 diabetes.Diabetes Medications
and
Cardiovascular Impact.Recommendations for management of diabetes
Cardiovascular safety of anti-diabetic drugs.
Imeglimin is a novel, first-in-class antidiabetic drug that targets mitochondrial function. It was shown to improve both insulin resistance and insulin secretion based on animal and human studies. Imeglimin received its first approval in Japan in 2021 based on positive results from the Phase III TIMES clinical trials program demonstrating its efficacy in lowering blood glucose levels and its safety both as monotherapy and in combination with other oral antidiabetic drugs or insulin. Imeglimin may also provide cardiovascular benefits given its effects on improving mitochondrial function in multiple tissues beyond just glycemic control.
- Correction insulin is preferable to sliding scale insulin for managing inpatient hyperglycemia as it treats current high blood sugars and prevents future highs through the use of basal, nutritional, and correctional insulin components.
- The case study patient should be started on correctional insulin therapy which includes initiation of basal insulin, nutritional insulin with meals, and additional correctional insulin for blood sugars over target.
- When initiating or adjusting insulin therapy in the hospital, consideration should be given to the patient's diabetes type and weight to determine the total daily insulin dose and regimen. Frequent monitoring and adjustments are important to achieve good glycemic control.
1) The document discusses insulin therapy for type 2 diabetes, providing cases of patients not achieving optimal blood sugar control on oral medications alone.
2) It recommends starting basal insulin alone for some patients or adding meal insulin to basal insulin for others based on blood sugar patterns.
3) Patient education materials and algorithms for self-titrating insulin are provided to help patients adjust insulin doses based on home blood sugar monitoring.
Dr. Vivek Baliga discusses diabetic dyslipidemia and emerging concepts in its management. Non-HDL cholesterol is a better indicator of cardiovascular risk than LDL cholesterol. It encompasses all potentially atherogenic lipoproteins. Dual PPAR alpha/gamma agonists like saroglitazar can effectively control dyslipidemia and maintain glycemic control in patients with diabetes by reducing triglycerides and non-HDL cholesterol while improving other lipid and glucose parameters. Saroglitazar is approved in India for the treatment of diabetic dyslipidemia.
This document provides information on managing diabetes in the intensive care unit (ICU). It discusses reasons for deteriorated glucose control during hospital admissions like stress hyperglycemia and corticosteroid therapy. It recommends maintaining blood glucose between 140-180 mg/dL based on studies showing increased mortality risks outside this range. Insulin protocols presented aim to gradually control hyperglycemia through hourly monitoring and titrating intravenous insulin doses based on blood glucose levels and rate of change.
This document discusses two case studies of patients with type 2 diabetes mellitus. For the first case, a 50-year old female patient with HbA1c of 8.5-9% on oral medications, the summary recommends starting basal insulin such as glargine or detemir 15-20 units at bedtime. For the second case, a 68-year old obese male patient with HbA1c of 10.5% on maximum oral medications, the summary recommends starting a total daily dose of insulin of 0.3-0.5 units/kg, starting with premixed insulin such as Mixtard 18/10 units. Both cases emphasize individualizing treatment targets and adjusting insulin doses based on self-
The document discusses guidelines for initiating insulin therapy in patients with type 2 diabetes not controlled on oral antidiabetic drugs (OADs). It recommends starting with either bedtime intermediate-acting insulin or bedtime or morning long-acting insulin, beginning at a dose of 10 units or 0.2 units/kg. The insulin dose is then titrated up based on fasting blood glucose levels until the target range is achieved. Additional injections of rapid-acting insulin may be added if pre-meal blood glucose levels remain out of range.
The document discusses different types of insulin available to manage diabetes, including rapid-acting, short-acting, intermediate-acting, long-acting, and premixed insulins. It reviews insulin protocols and addresses patient selection for different regimens. The document also discusses designing and adjusting insulin regimens, including using a basal-bolus approach to better mimic normal physiology.
Inpatient Diabetes Management - How to Control Hyperglycemia inhsopitalUsama Ragab
Inpatient Diabetes Management
By Dr. Usama Ragab Youssif
Lecturer of Medicine Zagazig University
Why we need this lecture?
Diabetes inhospital is common problem
Increased diabetes morbidities
Increased mortality
This document appears to be a slide presentation given by Dr. Faraz Farishta on diabetes management. It discusses diabetes as a global health problem and challenges in achieving optimal blood sugar control, including clinical inertia. It reviews guidelines on treatment goals and limitations of conventional oral therapies. It then discusses how DPP-4 inhibitors were developed to address multiple defects in type 2 diabetes by inhibiting the breakdown of GLP-1, an incretin hormone that stimulates insulin secretion. Data is presented on the efficacy and value of the DPP-4 inhibitor vildagliptin.
The document discusses inpatient management of hyperglycemia. It provides an overview of studies showing associations between hyperglycemia and poor outcomes in hospitalized patients. It then reviews interventional studies demonstrating that intensive insulin therapy targeting tighter glucose control can improve outcomes. The document discusses strategies for glucose management in the hospital, barriers to control, and different insulin regimens that can be used.
Recent studies have highlighted the growing global burden of type 2 diabetes, with over 600 million people projected to have the disease by 2045. In particular, Egypt will face explosive growth in cases. While control of blood sugar levels is important for reducing complications, most patients do not achieve treatment goals. Intensifying treatment in a timely manner when blood sugar is poorly controlled can reduce cardiovascular risks. Inertia on the part of both physicians and healthcare systems often limits timely treatment changes needed to improve outcomes for patients with type 2 diabetes.
This clinical trial involved 245 patients with type 2 diabetes who were randomized to receive either insulin degludec once daily, insulin degludec three times per week, or insulin glargine once daily, all in combination with metformin. The primary outcome was change in HbA1c levels after 16 weeks of treatment. The results showed that HbA1c levels were reduced from baseline in all treatment groups, with reductions of 1.3-1.5% and no significant differences between the groups. Fasting glucose levels and body weight changes were also similar across groups. This trial demonstrated that insulin degludec provided glycemic control comparable to insulin glargine with no increased safety risks, including with a dos
The UK Prospective Diabetes Study was a 20-year multicenter randomized controlled trial that investigated the effects of intensive glucose control and tight blood pressure control on diabetes complications. Over 5,000 patients with newly diagnosed type 2 diabetes were recruited between 1977-1991 and followed for a median of 10 years. The study found that intensive glucose control reduced the risk of diabetes complications, particularly microvascular complications, by 10-25%. The blood pressure control study found that tight blood pressure control reduced the risk of diabetes-related endpoints by 24% and strokes by 44% compared to less tight control.
The document discusses various types of insulin and insulin delivery methods for managing diabetes. It describes a 37-year-old man with type 1 diabetes of 18 years whose HbA1c is consistently high at 9.0-10.5% despite different insulin regimens. It then discusses options like Glargine insulin and education programs that can help improve blood sugar control and reduce hypoglycemia for patients.
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.
1) This document discusses the initiation and adjustment of insulin therapy for type 2 diabetes. It recommends starting with a long-acting basal insulin at bedtime and titrating the dose up gradually until fasting blood glucose is at target levels.
2) If HbA1c remains above 7% after 2-3 months, short-acting insulins should be added at mealtimes starting with breakfast. The doses are then titrated based on pre-meal blood glucose readings.
3) If HbA1c is still not at target after a further 2-3 months, a third daily insulin injection may be needed and post-meal blood glucose should be checked to guide adjustments. The goal is to approximate normal pancreatic
Imeglimin is a novel anti-diabetic drug that targets mitochondrial dysfunction, a key pathological basis for diabetes. It acts on the pancreas to preserve insulin secretion and on tissues to enhance insulin action. Imeglimin has shown efficacy in reducing HbA1c and fasting glucose when used alone or in combination with other drugs. It offers advantages over existing treatments by improving mitochondrial function without inhibiting respiration and has shown protective effects on organs like the kidney and heart. The risk of lactic acidosis may be lower compared to metformin due to distinct mechanisms of action.
The document summarizes the history and types of insulin. It describes the key discoveries in insulin's development, including the identification of the islets of Langerhans in 1869, the discovery that removing the pancreas causes diabetes in 1889, and the isolation of insulin from the pancreas by Banting and Best in 1922. It also discusses the different types of human and analog insulins, including rapid-acting, long-acting, premixed, and biosimilar insulins. The document emphasizes that insulin comes in various preparations that can be tailored to individual patient needs.
Cardiovascular safety of anti-diabetic drugs.Cardiovascular Outcome Trials ...magdy elmasry
Cardiologists and diabetes.Target organs and action mechanism of antidiabetic drugs.Cardiovascular Outcome Trials
( CVOTs ) in Diabetes.Completed and ongoing CVOTs in type 2 diabetes.Diabetes Medications
and
Cardiovascular Impact.Recommendations for management of diabetes
Cardiovascular safety of anti-diabetic drugs.
Imeglimin is a novel, first-in-class antidiabetic drug that targets mitochondrial function. It was shown to improve both insulin resistance and insulin secretion based on animal and human studies. Imeglimin received its first approval in Japan in 2021 based on positive results from the Phase III TIMES clinical trials program demonstrating its efficacy in lowering blood glucose levels and its safety both as monotherapy and in combination with other oral antidiabetic drugs or insulin. Imeglimin may also provide cardiovascular benefits given its effects on improving mitochondrial function in multiple tissues beyond just glycemic control.
- Correction insulin is preferable to sliding scale insulin for managing inpatient hyperglycemia as it treats current high blood sugars and prevents future highs through the use of basal, nutritional, and correctional insulin components.
- The case study patient should be started on correctional insulin therapy which includes initiation of basal insulin, nutritional insulin with meals, and additional correctional insulin for blood sugars over target.
- When initiating or adjusting insulin therapy in the hospital, consideration should be given to the patient's diabetes type and weight to determine the total daily insulin dose and regimen. Frequent monitoring and adjustments are important to achieve good glycemic control.
1) The document discusses insulin therapy for type 2 diabetes, providing cases of patients not achieving optimal blood sugar control on oral medications alone.
2) It recommends starting basal insulin alone for some patients or adding meal insulin to basal insulin for others based on blood sugar patterns.
3) Patient education materials and algorithms for self-titrating insulin are provided to help patients adjust insulin doses based on home blood sugar monitoring.
Dr. Vivek Baliga discusses diabetic dyslipidemia and emerging concepts in its management. Non-HDL cholesterol is a better indicator of cardiovascular risk than LDL cholesterol. It encompasses all potentially atherogenic lipoproteins. Dual PPAR alpha/gamma agonists like saroglitazar can effectively control dyslipidemia and maintain glycemic control in patients with diabetes by reducing triglycerides and non-HDL cholesterol while improving other lipid and glucose parameters. Saroglitazar is approved in India for the treatment of diabetic dyslipidemia.
This document provides information on managing diabetes in the intensive care unit (ICU). It discusses reasons for deteriorated glucose control during hospital admissions like stress hyperglycemia and corticosteroid therapy. It recommends maintaining blood glucose between 140-180 mg/dL based on studies showing increased mortality risks outside this range. Insulin protocols presented aim to gradually control hyperglycemia through hourly monitoring and titrating intravenous insulin doses based on blood glucose levels and rate of change.
This document discusses two case studies of patients with type 2 diabetes mellitus. For the first case, a 50-year old female patient with HbA1c of 8.5-9% on oral medications, the summary recommends starting basal insulin such as glargine or detemir 15-20 units at bedtime. For the second case, a 68-year old obese male patient with HbA1c of 10.5% on maximum oral medications, the summary recommends starting a total daily dose of insulin of 0.3-0.5 units/kg, starting with premixed insulin such as Mixtard 18/10 units. Both cases emphasize individualizing treatment targets and adjusting insulin doses based on self-
The document discusses guidelines for initiating insulin therapy in patients with type 2 diabetes not controlled on oral antidiabetic drugs (OADs). It recommends starting with either bedtime intermediate-acting insulin or bedtime or morning long-acting insulin, beginning at a dose of 10 units or 0.2 units/kg. The insulin dose is then titrated up based on fasting blood glucose levels until the target range is achieved. Additional injections of rapid-acting insulin may be added if pre-meal blood glucose levels remain out of range.
The document discusses different types of insulin available to manage diabetes, including rapid-acting, short-acting, intermediate-acting, long-acting, and premixed insulins. It reviews insulin protocols and addresses patient selection for different regimens. The document also discusses designing and adjusting insulin regimens, including using a basal-bolus approach to better mimic normal physiology.
Inpatient Diabetes Management - How to Control Hyperglycemia inhsopitalUsama Ragab
Inpatient Diabetes Management
By Dr. Usama Ragab Youssif
Lecturer of Medicine Zagazig University
Why we need this lecture?
Diabetes inhospital is common problem
Increased diabetes morbidities
Increased mortality
This document appears to be a slide presentation given by Dr. Faraz Farishta on diabetes management. It discusses diabetes as a global health problem and challenges in achieving optimal blood sugar control, including clinical inertia. It reviews guidelines on treatment goals and limitations of conventional oral therapies. It then discusses how DPP-4 inhibitors were developed to address multiple defects in type 2 diabetes by inhibiting the breakdown of GLP-1, an incretin hormone that stimulates insulin secretion. Data is presented on the efficacy and value of the DPP-4 inhibitor vildagliptin.
The document discusses inpatient management of hyperglycemia. It provides an overview of studies showing associations between hyperglycemia and poor outcomes in hospitalized patients. It then reviews interventional studies demonstrating that intensive insulin therapy targeting tighter glucose control can improve outcomes. The document discusses strategies for glucose management in the hospital, barriers to control, and different insulin regimens that can be used.
Recent studies have highlighted the growing global burden of type 2 diabetes, with over 600 million people projected to have the disease by 2045. In particular, Egypt will face explosive growth in cases. While control of blood sugar levels is important for reducing complications, most patients do not achieve treatment goals. Intensifying treatment in a timely manner when blood sugar is poorly controlled can reduce cardiovascular risks. Inertia on the part of both physicians and healthcare systems often limits timely treatment changes needed to improve outcomes for patients with type 2 diabetes.
This clinical trial involved 245 patients with type 2 diabetes who were randomized to receive either insulin degludec once daily, insulin degludec three times per week, or insulin glargine once daily, all in combination with metformin. The primary outcome was change in HbA1c levels after 16 weeks of treatment. The results showed that HbA1c levels were reduced from baseline in all treatment groups, with reductions of 1.3-1.5% and no significant differences between the groups. Fasting glucose levels and body weight changes were also similar across groups. This trial demonstrated that insulin degludec provided glycemic control comparable to insulin glargine with no increased safety risks, including with a dos
The UK Prospective Diabetes Study was a 20-year multicenter randomized controlled trial that investigated the effects of intensive glucose control and tight blood pressure control on diabetes complications. Over 5,000 patients with newly diagnosed type 2 diabetes were recruited between 1977-1991 and followed for a median of 10 years. The study found that intensive glucose control reduced the risk of diabetes complications, particularly microvascular complications, by 10-25%. The blood pressure control study found that tight blood pressure control reduced the risk of diabetes-related endpoints by 24% and strokes by 44% compared to less tight control.
The document discusses various types of insulin and insulin delivery methods for managing diabetes. It describes a 37-year-old man with type 1 diabetes of 18 years whose HbA1c is consistently high at 9.0-10.5% despite different insulin regimens. It then discusses options like Glargine insulin and education programs that can help improve blood sugar control and reduce hypoglycemia for patients.
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.
Several studies have compared basal-bolus insulin regimens using basal insulin plus oral agents to premixed insulin regimens in patients with type 2 diabetes:
- Studies found basal-bolus regimens were more effective at achieving glycemic targets and reducing HbA1c levels compared to premixed regimens.
- Basal-bolus regimens resulted in less hypoglycemia and weight gain.
- Physicians and patients reported greater treatment satisfaction with basal-bolus regimens due to their increased flexibility compared to fixed-ratio premixed regimens.
The document summarizes findings from the United Kingdom Prospective Diabetes Study (UKPDS), a long-term clinical trial that compared intensive versus conventional blood glucose control in patients newly diagnosed with type 2 diabetes. The UKPDS found that intensive glucose control through pharmacologic therapy (insulin, sulfonylureas, or metformin) reduced the risk of microvascular complications compared to conventional diet-based control. Intensive control also reduced the risk of macrovascular disease, though to a lesser extent and not significantly.
Insulin therapy involves various types of insulin preparations that aim to mimic the body's natural insulin secretion. Short-acting insulins like regular insulin have an onset of 30-60 minutes while rapid-acting analogs like aspart and lispro have an onset of 5-15 minutes. Intermediate-acting NPH insulin has an onset of 2 hours. Long-acting basal insulins like glargine and detemir aim to provide consistent insulin levels and have onset times of 2 hours with durations of 12-24 hours. Newer ultra-long acting insulins like degludec last over 40 hours with the goal of reducing hypoglycemia risk and glycemic variability compared to earlier insulin types.
2. Simplifying insulin therapy with Co-Formulation Insulin salinan-1 copy.pptxMuhammadAdriWansah1
This document summarizes the results of the STEP BY STEP trial which compared the efficacy and safety of insulin degludec/insulin aspart (Ryzodeg®) to insulin glargine U100 plus insulin aspart in patients with type 2 diabetes treated with basal insulin. The trial found that Ryzodeg® provided similar reductions in HbA1c from baseline to 26 weeks and 38 weeks compared to basal-plus, with fewer daily injections (1 vs 2). Ryzodeg® also resulted in significantly lower rates of nocturnal hypoglycemia over 38 weeks.
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 discusses the benefits of earlier insulinization for patients with type 2 diabetes. It provides evidence that introducing insulin therapy earlier in the disease process can help preserve pancreatic beta cell function and mass, leading to better long-term glycemic control and metabolic outcomes. The document reviews the mechanisms of beta cell dysfunction and failure in diabetes, and suggests that earlier insulin use can protect beta cells from glucotoxicity and lipotoxicity by inducing a period of rest. Clinical trials are cited showing improved glycemic control and remission of diabetes symptoms for up to 2 years with short-term intensive insulin therapy initiated early in the disease.
Based on the information provided:
- Patient has had type 2 diabetes for 15 years
- Current HbA1c is 8.5%, indicating suboptimal glycemic control
- He is post-MI, increasing his cardiovascular risk
- Current medications include metformin and sulfonylurea, but glycemic targets are not being met
The next appropriate step would be to initiate basal insulin therapy in addition to continuing the oral medications. Starting with a long-acting basal insulin like glargine once daily would help improve fasting glucose control and lower HbA1c while minimizing hypoglycemia risk. The oral agents could be continued to provide additional glycemic benefits. Basal insulin represents a relatively simple and effective way
Alpha glucosidase inhibitors work by reducing the breakdown of carbohydrates in the digestive tract, lowering the rise in blood glucose levels after meals. They are most effective when taken with meals containing carbohydrates. Common side effects include gastrointestinal issues like flatulence and diarrhea. Guidelines recommend alpha glucosidase inhibitors as an option for treating type 2 diabetes, either alone or in combination with other oral hypoglycemic agents or insulin, especially in patients at risk of hypoglycemia.
Alpha glucosidase inhibitors work by reducing the breakdown of carbohydrates in the digestive tract, lowering the rise in blood glucose levels after meals. They are most effective when taken with meals containing carbohydrates. Common side effects include gastrointestinal issues like flatulence and diarrhea. Guidelines recommend alpha glucosidase inhibitors as an option for treating type 2 diabetes, either alone or in combination with other oral hypoglycemic agents or insulin, especially in patients at risk of hypoglycemia.
The document reviews studies of new insulin products including Degludec (Tresiba), Degludec/Aspart (Ryzodeg), and Glargine (Basaglar). It finds that Degludec has a longer duration of action of over 42 hours and lower day-to-day variability compared to other long-acting insulins. Degludec/Aspart is found to reduce post-dinner blood glucose excursions and provide more stable nocturnal glycemia than Glargine. Basaglar is approved as the first follow-on biologic insulin and demonstrated comparable efficacy and safety to Glargine in clinical trials.
incretin based therapy of type 2 diabetes mellitus 1SoM
This document discusses the pathophysiology of type 2 diabetes and new therapies based on incretin hormones. It describes how both insulin resistance and relative insulin deficiency contribute to diabetes due to impaired beta cell function. Incretin hormones like GLP-1 enhance insulin secretion and reduce glucagon levels, but are broken down quickly. New therapies include incretin mimetics like exenatide that are resistant to breakdown and have the added benefit of weight loss. DPP-IV inhibitors allow the body's own GLP-1 to remain active for longer by preventing its breakdown, and are weight neutral oral therapies like sitagliptin and vildagliptin that have few side effects. These new incretin based therapies improve
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,
This document summarizes key information about DPP-4 inhibitors for the treatment of type 2 diabetes. It begins by outlining the growing prevalence of diabetes worldwide and in the Middle East/North Africa. It then discusses the pathophysiology of type 2 diabetes, focusing on the incretin defect and role of DPP-4 inhibitors. The document reviews the mechanisms of action, selectivity profiles, and pharmacokinetic differences between various DPP-4 inhibitors. Head-to-head trials demonstrate comparable efficacy of sitagliptin versus sulfonylureas, with sitagliptin showing much lower risk of hypoglycemia. The document concludes DPP-4 inhibitors are effective options for glycemic control with a
- A 1-year randomized study examined the effects of consuming 500 ml of raw camel milk per day as an adjunct to routine diabetic management in type 1 diabetes patients.
- Patients who consumed raw camel milk had significant reductions in HbA1c, blood glucose, and necessary insulin dose compared to baseline. There were no significant changes in these measures for the control group receiving only routine management.
- The results suggest that raw camel milk consumption may help maintain long-term glycemic control and reduce insulin requirements for type 1 diabetes patients.
This 1-year randomized study examined the effects of consuming raw camel milk daily in addition to routine diabetic management for type 1 diabetes patients. 12 patients consumed 500ml of raw camel milk per day while 12 patients received only routine care. Both groups had adjustments to their insulin doses to maintain blood sugar levels. Patients consuming camel milk saw a significant reduction in HbA1c, average blood sugar, and necessary insulin dose compared to baseline. There were no significant side effects reported from camel milk consumption. The study suggests that raw camel milk may help improve glycemic control and reduce insulin needs for type 1 diabetes patients when used as an adjunct to insulin therapy.
1) The document discusses the incretin effect and how it is diminished in patients with type 2 diabetes. It also reviews the mechanisms of action and protraction of the GLP-1 receptor agonist Liraglutide.
2) Guidelines position Liraglutide as an effective add-on therapy to metformin for the treatment of type 2 diabetes, with efficacy in lowering A1c and promoting weight loss.
3) Clinical trials demonstrate Liraglutide significantly reduces A1c by up to 1.6% and promotes weight loss of up to 7.7 kg on average in a quartile of patients when used as an add-on therapy to metformin.
Dynamic endocrine tests involve stimulating or suppressing hormonal axes to assess endocrine function. Dr. Sahana discusses several key dynamic tests, including:
1. The Insulin Tolerance Test which triggers GH and ACTH release to assess pituitary function.
2. The Synacthen Test which uses ACTH to assess adrenal response and diagnose adrenal insufficiency.
3. Growth Hormone stimulation tests like the Insulin Tolerance Test which provoke GH release to diagnose growth hormone deficiency.
4. The Water Deprivation Test which restricts fluid intake to raise osmolality and assess ADH response, diagnosing diabetes insipidus.
1. The abdomen is the best site for insulin injection, with the outer thigh and upper arm as alternatives. Sites should be rotated to avoid lipodystrophy.
2. To inject insulin, the skin should be cleaned and gently pinched before inserting the needle at a 90 or 45 degree angle and slowly injecting the insulin while counting to 10 before removing the needle.
3. Used needles should be properly disposed of to prevent accidental needle sticks and protect sanitation workers and pets.
This document discusses injectable therapies for diabetes mellitus, including insulins and GLP1 receptor agonists. It describes the different types of insulin, their structures and indications. Short, rapid, intermediate and long-acting insulins are classified based on their time of administration and time-action profiles. Insulin regimens including basal-only, basal-plus, premixed and basal-bolus are covered. Adverse effects of insulin like lipodystrophy and the technique for administering injections are also summarized. Finally, GLP1 receptor agonists are classified based on their half-lives and the mechanisms, benefits, indications and adverse effects of this class are briefly discussed.
Growth hormone deficiency (GHD) is an important cause of short stature in children. Accurate diagnosis requires auxology, measurement of IGF1 and IGFBP3 levels, and GH stimulation tests. Recombinant human growth hormone therapy is effective and safe for treating GHD, but requires regular monitoring to ensure optimal results and growth responses.
This document discusses thyroid dysfunction in critical care settings. It describes a case of a 61-year-old man admitted to the ICU for decompensated CHF who had an altered mental status and abnormal thyroid function tests. Specifically, his TSH was elevated at 13 while his free T4 was normal but T3 was low. This pattern is characteristic of non-thyroidal illness (NTI) or sick euthyroid syndrome, rather than primary hypothyroidism. The document then reviews thyroid physiology, deiodinases, alterations in thyroid hormones that occur in NTI versus primary or central hypothyroidism, and outcomes of thyroid hormone replacement studies in critical illness.
Ernest Henry Starling and Sir William Maddock Bayliss were English physiologists in the early 20th century. In 1902, they discovered the hormone secretin, the first hormone to be identified, by showing that acid in the duodenum activates a substance that stimulates pancreatic secretions. In 1905, Starling introduced the term "hormone" to describe these chemical messengers that travel through the bloodstream to affect distant organs. Their discovery of secretin and definition of hormones established the field of endocrinology and marked a major advance in understanding the body's chemical signaling systems.
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdfrightmanforbloodline
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Travel Clinic Cardiff: Health Advice for International TravelersNX Healthcare
Travel Clinic Cardiff offers comprehensive travel health services, including vaccinations, travel advice, and preventive care for international travelers. Our expert team ensures you are well-prepared and protected for your journey, providing personalized consultations tailored to your destination. Conveniently located in Cardiff, we help you travel with confidence and peace of mind. Visit us: www.nxhealthcare.co.uk
Lecture 6 -- Memory 2015.pptlearning occurs when a stimulus (unconditioned st...AyushGadhvi1
learning occurs when a stimulus (unconditioned stimulus) eliciting a response (unconditioned response) • is paired with another stimulus (conditioned stimulus)
10 Benefits an EPCR Software should Bring to EMS Organizations Traumasoft LLC
The benefits of an ePCR solution should extend to the whole EMS organization, not just certain groups of people or certain departments. It should provide more than just a form for entering and a database for storing information. It should also include a workflow of how information is communicated, used and stored across the entire organization.
5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
It is hypothesised to regulate hunger, emotions, motor, cognitive, and autonomic processes.
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Co-Chairs, Val J. Lowe, MD, and Cyrus A. Raji, MD, PhD, prepared useful Practice Aids pertaining to Alzheimer’s disease for this CME/AAPA activity titled “Alzheimer’s Disease Case Conference: Gearing Up for the Expanding Role of Neuroradiology in Diagnosis and Treatment.” For the full presentation, downloadable Practice Aids, and complete CME/AAPA information, and to apply for credit, please visit us at https://bit.ly/3PvVY25. CME/AAPA credit will be available until June 28, 2025.
low birth weight presentation. Low birth weight (LBW) infant is defined as the one whose birth weight is less than 2500g irrespective of their gestational age. Premature birth and low birth weight(LBW) is still a serious problem in newborn. Causing high morbidity and mortality rate worldwide. The nursing care provide to low birth weight babies is crucial in promoting their overall health and development. Through careful assessment, diagnosis,, planning, and evaluation plays a vital role in ensuring these vulnerable infants receive the specialize care they need. In India every third of the infant weight less than 2500g.
Birth period, socioeconomical status, nutritional and intrauterine environment are the factors influencing low birth weight
Summer is a time for fun in the sun, but the heat and humidity can also wreak havoc on your skin. From itchy rashes to unwanted pigmentation, several skin conditions become more prevalent during these warmer months.
1. Basal Insulin- A
breakthrough in Insulin
Therapy Dr. Pranab Kumar Sahana
Associate Professor
Department of Endocrinology
NilRatan Sircar Medical College
Kolkata
2. First Human Patient
On Jan. 11, 1922, 14-year-old Leonard Thompson
was the first human patient to receive insulin
made by Banting and Best.
Leonard's blood glucose dropped to normal, and
he began to gain weight.
4. Normal Pancreatic Function
Meal Meal Meal
Prandial: At mealtime,
insulin is rapidly released
in response to food.
Basal: Beta cells secrete
small amounts of insulin
throughout the day.
Basal Insulin
Bolus Insulin
*Insulin effect images are theoretical representations and are not derived from clinical trial data.
5. Short Comings on Animal
Insulins
• Impurity
• Antigenecity
• Allergic reaction
6. Shortfalls of Regular Human Insulin (1978)
• Short acting in nature( 6-8 hours).
• Multiple daily injections to match physiological release
pattern.
• Less treatment satisfaction.
• Unpredictable Hypoglycemia
8. Neutral Protamine Hagedorn
(1940-50)
• Hans Christian Hagedorn in 1936 added
protamine from trout semen to insulin.
• Protamine is a highly bsaic protein
• Later Zinc was added to stabilize the complex
• Leads to microprecipitation and delayed
absorption and prolonged duration of action
• 1950 Nordisk markets NPH Insulin
10. Rationality of Basal Insulin
• Basal insulin supresses hepatic glucose
output and also lipolysis between meals
and in night
• Prevents Ketoacidosis in Type 1
• Most individuals with type 2 diabetes will
achieve adequate glycemic control with
the addition of basal insulin alone
ADA/EASD 2015, IDF, NICE 2014
11. Benefits of NPH Insulin
• Effective
• Useful in Dawn phenomenon
• Safe in pregnancy, children
12. Limitations of NPH
Do not mimic basal insulin profile
– Variable absorption and action
– Pronounced peaks
– Action profile depends on dose
– Risk of nocturnal and unpredictable hypoglycemia
– Less than 24-hour duration of action
– More weight gain
13. Ideal Basal Insulin
13
• Mimics normal pancreatic basal insulin secretion
• Long-lasting effect around 24 hours
• Smooth, peak less profile
• Reproducible and predictable effects
• Reduced risk of nocturnal hypoglycaemia & weight gain
• Once-daily administration for convenience
• Flexible meal timings
Hawkins M, et al. Joslin's Diabetes mellitus. 14th Edition. Lippincott Williams and Wilkins. 2000:426–448
14. Insulin Glargine (2000)
• Modifications to human insulin chain
– Substitution of glycine at position A21
– Addition of 2 arginines at position B30
• Gradual release pattern from injection site
• Peakless, long-lasting insulin profile
1 5 10 15 20 25 30
1 5 10 15 20Asp
Gly
Arg
Extension
Substitution
Arg
15. 15
Clear
solution
pH 4.0
S.C. Injection of
an acidic solution (pH 4.0)
Glargine: First 24-h
rDNA basal insulin
analogue in clinical
practice
Capillary Membrane
Insulin in Blood
Dissolution
Hexamers Dimers Monomers
10-3
M 10-5
M 10-8
M
Slow dissolution of free
glargine hexamers from
precipitated Glargine
Protracted action
Insulin Glargine
1) McKeage K et al. Drugs. 2001;61:1599-1624, 2) Campbell RK et al Clin Ther. 2001; 23(12):1938-1957, 3) Wang F et al Clin Ther. 2003;25:1541-1577.
16. Once-daily insulin Glargine has consistently demonstrated
efficacy in helping type 2 diabetes patients achieve target
glycaemic control
EASIE9
(n=480)
24 weeks
TULIP1
(n=211)
36 weeks
INSIGHT2
(n=405)
24 weeks
TTT3
(n=764)
24 weeks
APOLLO4
(n=412)
44 weeks
LAPTOP5
(n=364)
24 weeks
TRIPLE6
(n=216)
24 weeks
LANMET7
(n=110)
36 weeks
L2T38
(n=973)
24 weeks
In clinical efficacy studies using a target FPG <5.6 mmol/L and comparing Glargine® /OADs vs. different comparators, T2DM patients were
well controlled on Lantus® treatment with a low rate of hypoglycaemia and well-characterised adverse event profile
T2DM
Baseline HbA1c
Endpoint HbA1c
1. Blicklé JF, et al. Diabetes Obes Metab 2009;11:379-386
2. Gerstein HC, et al. Diabetes Med 2006;23:736-742
3. Riddle MC, et al. Diabetes Care 2003;26:3080-3086
4. Bretzel RG, et al. Lancet 2008;371:1073-1084
5. Janka HU, et al. Diabetes Care 2005;28:254-259
6. Rosenstock J, et al. Diabetes Care 2006;29:554-549
7. Yki-Järvinen H, et al. Diabetologia 2006;49:442-451
8. Swinnen SG, et al. Diabetes Care 2010;33:1176-1178
9. Aschner P, et al. Lancet 2012;379:2262-2269
BOT, basal insulin-supported oral therapy
OAD, oral antidiabetic drugs
Consistent achievement of HbA1c targets (or close to it)
when Glargine was added to type 2 patients uncontrolled
on OAD treatment (BOT regimens)
17. HbA1c reductions with once-daily insulin Glargine in controlled
trials of varying duration and size in type 1 diabetes
1. Raskin P, et al. Diabetes Care 2000;23:1666-1671
2. Bolli GB, et al. Nutr Metab Cardiovasc Dis 2009;19:571-579
3. Fulcher GR, et al. Intern Med J. 2005;35:536-542
4. Ashwell SG, et al. Diabet Med 2006;23:285-292
5. Chatterjee S, et al. Diabetes Res Clin Pract 2007;77:215-222
6. Porcellati F, et al. Diabet Med 2004;21:1213-1220
T1DM
Raskin
(2000)1
(n=619)
16 weeks
Bolli
(2009)2
(n=175)
30 weeks
Fulcher
(2005)3
(n=125)
30 weeks
Ashwell
(2006)4
(n=56)
32 weeks
Chatterjee
(2007)5
(n=53)
36 weeks
Porcellati
(2004)6
(n=121)
52 weeks
Baseline HbA1c
Endpoint HbA1c
Once-daily Glargine has demonstrated effective
HbA1c reductions across a wide range of randomised
controlled trials in type 1 diabetes
18. Hypoglycemia defined as plasma glucose ≤72 mg/dL
*P<0.05 vs insulin glargine.
NPH=neutral protamine Hagedorn
Adapted from Riddle M et al. Diabetes Care. 2003;26:3080-3086. Used with permission.
0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
20 22 24 2 4 6 8 10 12 14 16 18
Time of day (h)
*
*
*
*
*
*
*
Glargine
NPH
Basal
insulin
Breakfast Lunch Dinner
Eventsperpatientexposure–year
Symptomatic Hypoglycemic Events
19. 19
Limitations of Insulin Glargine
• It can not be mixed with other short/rapid acting insulins
as the pH of the formulation is acidic.
• Initially it may produce burning sensation due to acidic
pH.
ADA Practical Insulin: A handbook for prescribing providers. 3rd
ed., Heise T et al. Diabetes 2004; 53(6): 1614-1620
21. Insulin detemir versus insulin glargine for type 2
diabetes mellitus.
Swinnen SG1
, Simon AC, Holleman F, Hoekstra
JB, Devries JH.
• there is no clinically relevant difference in efficacy or
safety between insulin detemir and insulin glargine
for targeting hyperglycaemia. However, to achieve
the same glycaemic control insulin detemir was often
injected twice-daily in a higher dose but with less
weight gain, while insulin glargine was injected once-
daily, with somewhat fewer injection site reactions.
Cochrane Database Syst Rev. 2011 Jul 6;(7)
22. Insulin degludec (2013)
Rationally designed, beyond sequence modification
Jonassen I et al. Pharm Res 2012;29:2104–2114.
N
H
O
OH
O NH
O
OH
O
DesB30 insulin
DesB30
T
Des(B30) LysB29(γ-Glu Nε-hexadecandioyl) human insulin
s
s
s
s
A1
B1
A21
s s
L-γ-Glu
Glutamic acid
‘spacer’
N
H
O
OH
O NH
O
Hexadecandioyl
Fatty diacid side
chain
23. Degludec : Mode of Action of
(Retarded Absorption)
Insulin degludec for injection is a
zinc/phenol formulation in the T3R3
conformation as di-hexamers (~69 kDa)
Zinc diffuses slowly causing
individual hexamers to disassemble,
releasing dimers and then monomers
Monomers are absorbed from
the depot into the circulation
- Phenol
Monomers bound to albumin
(protein-bound depot)
Rapid phenol depletion (after injection)
changes the conforation to a T6-state
exposing the core and Zinc ions and
multi-hexamer chains are formed
- Zinc
multi-hexamer chains
24. Flexible Dosing Schedule of Degludec
morning
Mon Tue Wed Thu Fri Sat Sun
morning morning
evening evening evening evening
40h 40h 40h
8h 8h
24h
Dosing schedule provided for a maximum dosing
interval of 40 hrs & a minimum doisng interval of 8
hrs.
Birkeland et al. IDF 2011:P-1443; Bain et al. IDF 2011:O-0508; Birkeland et al. Diabetologia 2011;54(suppl. 1):S423;
Atkin et al. Diabetologia 2011;54(suppl. 1):S53; Meneghini et al. Diabetes 2011;60(suppl. 1A):LB10 (NN1250-3668)
27. Insulin Glargine vs. Insulin Detemir
vs. NPH insulin
Aspects Parameters
Insulin
Glargine
Insulin
Detemir
NPH
Insulin
Efficacy & Safety
FPG reduction - - -
HbA1c reduction - - -
Hypoglycaemia + + ++
Weight gain + neutral ++
Long term
efficacy
+ + +
Pharmacoeconomics Cost of therapy ++ +++ +
27
1) Hedrington MS, et al. Diabetes Technol Ther. 2011;13(Suppl 1):S33-42, 2) Pfohl M et al., Health Outcomes Research in Medicine. 2011;2(1):e39-e50
28. SWITCH – trial design
IDeg, insulin degludec; Iglar (U100); NN Trial ID NN1250-3998 and 3995
Trial information
•Double-blind
•Cross-over
•Treat-to-target
•Randomised 1:1and
50/50 AM/PMMaintenance
phase
16 weeks
Maintenance
phase
16 weeks
IGlar OD ± OADs
IDeg OD ± OADs
Titration
phase
16 weeks
IGlar OD ± OADs
IDeg OD ± OADs
Titration
phase
16 weeks
Treatment period 1 Treatment period 2
721 patients
•Age ≥18 years
•T2D ≥26 weeks
•Basal insulin ± OADs
•HbA1c ≤9.5%
•BMI ≤45 kg/m2
To reduce the risk of hypoglycaemia in the
first treatment month, the overall daily
dose of basal insulin was reduced by 20%
at randomisation for subjects treated
with pre-trial BID basal insulin.
Trial information
•Double-blind
•Cross-over
•Treat-to-target
•Randomised 1:1and
50/50 AM/PMMaintenance
period
16 weeks
Maintenance
period
16 weeks
IGlar U100 OD ± IAsp
IDeg OD ± IAsp
Titration
period
16 weeks
IGlar U100 OD ± IAsp
IDeg OD + IAsp
Titration
period
16 weeks
Treatment period 1 Treatment period 2
Basal titration (IDeg and IGlar U100)
•Once-weekly titration based on lowest of 3 consecutive days
•Target: 4.0–5.0 mmol/L (71–90 mg/dL) measurements
• 20% dose reduction at randomisation
and at switch for all patients
SWITCH2SWITCH1
29. Non inferiority in HbA1c over timeIDeg
IGlar U100
Titration period 1 Maintenance period 1 Titration period 2 Maintenance period 2
Treatment period 1 Treatment period 2
0.0 0.0
Estimated treatment difference:
0.09% [95% CI -0.04;0.23]
Non-inferiority confirmed
032
CROSS-OVER
Mean±SEM; FAS; Observed data; NN1250-3998 and NN1250-3995; Cross-over IDeg vs IGlar U100 in T2DM and T1DM
SWITCH2SWITCH1
Estimated treatment difference:
0.03% [95% CI -0.10;0.15]
Non-inferiority confirmed
Estimated treatment difference:
0.11% [95% CI -0.00;0.23]
Non-inferiority confirmed
0.0 0.0
30. IDeg
IGlar
0.5
0.0
0.9
0.7
0.4
0.1
0.8
0.6
0.3
0.2
3216 20 24 3018 22 26 28
Time (weeks)*
30% lower
with IDeg
(significant)
IDeg: 186 events/100 PYE
IGlar: 265 events/100 PYE
IDeg
IGlar
4.5
0.0
8.1
6.3
3.6
0.9
7.2
5.4
2.7
1.8
3216 20 24 3018 22 26 28
Time (weeks)*
11% lower
with IDeg
(significant)
IDeg: 2201 events/100 PYE
IGlar: 2463 events/100 PYE
Severe or BG confirmed symptomatic
hypoglycaemia – maintenance phase (rates)
T2DM
T1DM
*Combined maintenance phases of treatment period 1 and 2 (week
16-32 and 48-64)
PYE, patient-years of exposure; *Combined maintenance phases of
treatment period 1 and 2 (week 16-32 and 48-64)
IDeg IGlar U100
Proportio
n
(%
patients)
Rate
(episodes/
100 PYE)
Proportio
n
(%
patients)
Rate
(episodes/
100 PYE)
22.5% 185.6 31.6% 265.4
IDeg IGlar U100
Proportio
n
(%
patients)
Rate
(episodes/
100 PYE)
Proportio
n
(%
patients)
Rate
(episodes/
100 PYE)
77.3% 2200.9 79.9% 2462.7
p<0.0001
p<0.0001
31. IDeg
IGlar
0.16
0.00
0.32
0.24
0.12
0.04
0.28
0.20
0.08
3216 20 24 3018 22 26 28
Time (weeks)*
42%
lower
with IDeg
(significant)
IDeg: 55 events/100 PYE
IGlar: 94 events/100 PYE
IDeg
IGlar
0.6
0.0
1.1
0.9
0.4
0.1
1.0
0.7
0.3
0.8
0.5
0.2
3216 20 24 3018 22 26 28
Time (weeks)*
36% lower
rate with IDeg
(significant)
IDeg: 277 events/100 PYE
IGlar: 429 events/100 PYE
Severe or BG confirmed symptomatic
nocturnal hypoglycaemia –maintenance phase
*Combined maintenance phases of treatment period 1 and 2
(week 16-32 and 48-64)
*Combined maintenance phases of treatment period 1 and 2
(week 16-32 and 48-64)
T2DM T1DM
IDeg IGlar U100
Proportio
n
(%
patients)
Rate
(episodes/
100 PYE)
Proportio
n
(%
patients)
Rate
(episodes/
100 PYE)
9.7% 55.2 14.7% 93.6
IDeg IGlar U100
Proportio
n
(%
patients)
Rate
(episodes/
100 PYE)
Proportio
n
(%
patients)
Rate
(episodes/
100 PYE)
32.8% 277.1 43.1% 428.6
p<0.0001 p<0.0001
32. Glargine U300
• New Insulin Glargine 300 Units/mL Versus
Glargine 100 Units/mL in People With Type 2
Diabetes Using Basal and Mealtime Insulin:
Glucose Control and Hypoglycemia in a 6-
Month Randomized Controlled Trial (EDITION
Diabetes Care 2014 Oct; 37(10): 2755-2762.
36. Continuing innovation with new basal insulin-
longer half life and lower variability
NPH, neutral protamine Hagedorn. Kalra. J Pak Med Assoc 2013;63:1442–4; Insulatard SmPC: http://www.medicines.org.uk/emc/medicine/3512/SPC/Insulatard+100+IU+ml,+Insulatard+Penfill+100+IU+ml,+Insulatard+InnoLet+100+IU+ml#
PHARMACOLOGICAL_PROPS; Toujeo SmPC: https://www.medicines.org.uk/emc/medicine/30586#PHARMACOLOGICAL_PROPS (All accessed September 2016)
Animal
insulin
preparations
Basal insulin
analogues
Isolation of insulin
(Banting & Best)
Ultra-long-acting basal
insulin
analogues
NPH insulin
HighHigh
Half life (hours):
Variability: MediumMedium LowLow
λλ 5–105–10 12.512.5 252518–1918–19
Insulin glargine
U300
Insulin detemir Insulin degludec
Insulin glargine
U100
37. Summary
• long-acting insulin analogs (insulin glargine and insulin detemir) are not
superior to NPH insulin in efficacy terms as determined by the number of
participants reaching HbA1c targets.
• Compared with use of NPH insulin, the use of the standard long-acting
insulin analogs with relatively flat action profiles is associated with up to a
50% reduced risk of nocturnal hypoglycemia.
• Basal insulin is now the cornerstone of insulin regime in Diabetes.
• It is convenient, effective ,less hypoglycemia.
• Glargine for all practical purposess is the gold standard basal insulin.
• Frequent monitoring, patient education is also integral part.
• Proper injection technique should be taught.
• Basal insulin have to supplemented with prandial insulin in Type 1 DM and
selected cases of Type T2 DM.
• In pregnancy, NPH and Detemir are recommended basal insulins.
Editor's Notes
Ensure audience understands normal basal insulin secretion
Discussion points
The ideal insulin regimen should strive to match normal insulin secretion patterns.
This includes;
A basal component that covers basal glucose levels throughout the day.
Bolus components that cover glucose excursions due to meals.
In insulin detemir, a 14-carbon (myristic acid) FA side chain is attached to Lysine at residue B29, with threonine at residue B30 removed.
Insulin detemir takes its name from: Des threonine + myristic (mir) acid
The amino acid sequence is identical to human insulin except for removal of threonine at B30.
At B29, a glutamic acid spacer is attached that bridges to a 16-carbon diacid.
Switch 1: Confirmation of non-inferiority in HbA1c reduction was a prerequisite for conducting the hypoglycaemia analyses.
The pre-requisite of achieving HbA1c non-inferiority in both treatment periods was met; estimated treatment difference (ETD) in treatment period 1: 0.03 %-points [–0.10; 0.15]95% CI. In treatment period 2, the ETD was 0.11%-points [–0.00; 0.23]95% CI.
Mean HbA1c at the end of treatment period 1 was 6.92% (IDeg) versus 6.78% (IGlar), and at the end of treatment period 2 was 6.95% (IDeg) versus 6.97% (IGlar).
Switch 2: The prerequisite of achieving non-inferiority for change in HbA1c in both treatment periods was met.
Mean HbA1c at the end of treatment period 1 was 7.06% (IDeg) versus 6.98% (IGlar), and at the end of treatment period 2 was 7.08% (IDeg) versus 7.11% (IGlar).
Switch 2: Superiority for the primary endpoint was achieved (30% lower rate of severe or BG-confirmed symptomatic hypoglycaemia; p&lt;0.0001) with IDeg versus IGlar.
Switch 1: Non-inferiority and superiority for the primary endpoint was achieved (significant 11% lower rate of severe or BG-confirmed symptomatic hypoglycaemia with IDeg vs. IGlar) in the maintenance periods.
Switch 2: Superiority for the secondary endpoint of the number of severe or BG-confirmed symptomatic nocturnal hypoglycaemic episodes was also achieved (42% reduction; p&lt;0.0001) for IDeg versus IGlar.
Switch 1: Non-inferiority and superiority were also achieved for the secondary endpoint of the number of severe or BG-confirmed symptomatic nocturnal hypoglycaemic episodes in the maintenance periods (significant 36% reduction) for IDeg vs. IGlar.
Clinical measures during treatment in the mITT population by visit and with last observation carried forward (LOCF). A: HbA1c. B: FPG. C: Daily basal insulin and mealtime insulin dosage.
Cumulative mean numbers of confirmed (plasma glucose ≤3.9 mmol/L [70 mg/dL]) or severe hypoglycemic events per participant during the main 6-month treatment period in the safety population. A: Nocturnal events. B: Events at any time of day or night (24 h).
Thus, there have been consistent efforts in developing newer insulins with a longer half life and a lower glycemic variability.