This document outlines learning objectives related to the management of type 2 diabetes with basal insulin and GLP-1 receptor agonists (GLP-1RAs). It describes the role of these medications per current guidelines and compares the benefits of adding GLP-1RAs versus prandial insulin to basal insulin. It also describes outcomes from fixed-ratio basal insulin/GLP-1RA combination products. Case scenarios are then presented to demonstrate potential treatment approaches discussed.
This document discusses glucose-lowering therapies and the clinical place of SGLT2 inhibitor agents. It presents the case of a 52-year-old male patient with type 2 diabetes, hypertension, and coronary artery disease. It analyzes adding empagliflozin or sitagliptin to the patient's current metformin regimen and reviews long-term trial data showing empagliflozin's superior effects on HbA1c reduction, weight loss, and hypoglycemia risk reduction compared to glimepiride. The document also discusses empagliflozin's benefits on blood pressure and potential cardioprotective mechanisms of action beyond glycemic control such as reducing cardiac fibrosis. It emphasizes the importance of individual
This document discusses the use of SGLT2 inhibitors (SGLT2i) in managing diabetes. It presents three case studies of patients with diabetes and cardiovascular complications who may benefit from SGLT2i treatment. It summarizes clinical trial data showing that empagliflozin lowers HbA1c, fasting plasma glucose, body weight, and blood pressure compared to other antidiabetic drugs. Empagliflozin also reduces visceral and subcutaneous fat. The document concludes that SGLT2i like empagliflozin provide glycemic control and cardiovascular benefits and can be considered as an addition to metformin for treating diabetes.
1) Exenatide once weekly (QW), also known as Bydureon, provides glycemic control through reductions in HbA1c of 1.3-1.9% over 24-30 weeks according to clinical trials.
2) Head-to-head trials show Exenatide QW results in similar or greater HbA1c reductions and more weight loss compared to other GLP-1 receptor agonists such as liraglutide.
3) Exenatide QW has been shown to maintain glycemic control over the long term with reductions in HbA1c of 1.5% maintained out to 6 years, along with significant and sustained weight loss from
The document discusses type 2 diabetes and the role of incretin hormones like GLP-1 and GIP. It notes that patients with type 2 diabetes have impaired secretion and actions of incretins. Dipeptidyl peptidase-4 (DPP-4) inhibitors work by blocking the degradation of incretins, thereby increasing their levels and effects. Clinical trials show that sitagliptin (Januvia), a DPP-4 inhibitor, improves glycemic control in type 2 diabetes patients by enhancing the actions of endogenous GLP-1 and GIP.
GENETIC DIET- Maria vranceanu dubai nutrition conferenceMARIA VRANCEANU
This 2-year study compared the effects of a ketogenic diet versus a nutrigenetic diet on weight loss and clinical parameters in 114 obese subjects. The nutrigenetic diet was personalized based on each subject's genetic test results. After 2 years, the nutrigenetic group had greater BMI loss (25.03% vs 17.62%), larger decreases in total cholesterol and blood glucose, and higher HDL levels compared to the ketogenic group. The study concludes that a nutrigenetically matched diet may be more effective than a standard ketogenic diet for long-term weight management and improvement of metabolic health markers.
This document discusses glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and compares them to other diabetes medications. It provides an overview of GLP-1 RAs, noting they are more effective at lowering A1C than other classes but also carry a lower risk of hypoglycemia. The document compares specific GLP-1 RAs such as liraglutide, exenatide, and lixisenatide, noting they differ in terms of amino acid homology to human GLP-1 and risk of antibody formation. DPP-4 inhibitors are also discussed and shown to result in lower GLP-1 levels than exogenous GLP-1 analog administration.
This document discusses glucose-lowering therapies and the clinical place of SGLT2 inhibitor agents. It presents the case of a 52-year-old male patient with type 2 diabetes, hypertension, and coronary artery disease. It analyzes adding empagliflozin or sitagliptin to the patient's current metformin regimen and reviews long-term trial data showing empagliflozin's superior effects on HbA1c reduction, weight loss, and hypoglycemia risk reduction compared to glimepiride. The document also discusses empagliflozin's benefits on blood pressure and potential cardioprotective mechanisms of action beyond glycemic control such as reducing cardiac fibrosis. It emphasizes the importance of individual
This document discusses the use of SGLT2 inhibitors (SGLT2i) in managing diabetes. It presents three case studies of patients with diabetes and cardiovascular complications who may benefit from SGLT2i treatment. It summarizes clinical trial data showing that empagliflozin lowers HbA1c, fasting plasma glucose, body weight, and blood pressure compared to other antidiabetic drugs. Empagliflozin also reduces visceral and subcutaneous fat. The document concludes that SGLT2i like empagliflozin provide glycemic control and cardiovascular benefits and can be considered as an addition to metformin for treating diabetes.
1) Exenatide once weekly (QW), also known as Bydureon, provides glycemic control through reductions in HbA1c of 1.3-1.9% over 24-30 weeks according to clinical trials.
2) Head-to-head trials show Exenatide QW results in similar or greater HbA1c reductions and more weight loss compared to other GLP-1 receptor agonists such as liraglutide.
3) Exenatide QW has been shown to maintain glycemic control over the long term with reductions in HbA1c of 1.5% maintained out to 6 years, along with significant and sustained weight loss from
The document discusses type 2 diabetes and the role of incretin hormones like GLP-1 and GIP. It notes that patients with type 2 diabetes have impaired secretion and actions of incretins. Dipeptidyl peptidase-4 (DPP-4) inhibitors work by blocking the degradation of incretins, thereby increasing their levels and effects. Clinical trials show that sitagliptin (Januvia), a DPP-4 inhibitor, improves glycemic control in type 2 diabetes patients by enhancing the actions of endogenous GLP-1 and GIP.
GENETIC DIET- Maria vranceanu dubai nutrition conferenceMARIA VRANCEANU
This 2-year study compared the effects of a ketogenic diet versus a nutrigenetic diet on weight loss and clinical parameters in 114 obese subjects. The nutrigenetic diet was personalized based on each subject's genetic test results. After 2 years, the nutrigenetic group had greater BMI loss (25.03% vs 17.62%), larger decreases in total cholesterol and blood glucose, and higher HDL levels compared to the ketogenic group. The study concludes that a nutrigenetically matched diet may be more effective than a standard ketogenic diet for long-term weight management and improvement of metabolic health markers.
This document discusses glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and compares them to other diabetes medications. It provides an overview of GLP-1 RAs, noting they are more effective at lowering A1C than other classes but also carry a lower risk of hypoglycemia. The document compares specific GLP-1 RAs such as liraglutide, exenatide, and lixisenatide, noting they differ in terms of amino acid homology to human GLP-1 and risk of antibody formation. DPP-4 inhibitors are also discussed and shown to result in lower GLP-1 levels than exogenous GLP-1 analog administration.
1) Current diabetes treatments often fail to achieve glycemic targets over time and treatment related issues like weight gain and hypoglycemia can decrease tight glycemic control.
2) HbA1c alone does not provide a full picture of glycemic fluctuations and both fasting and post-prandial glucose need to be addressed.
3) A more comprehensive approach is needed to glycemic management that minimizes weight gain and hypoglycemia and achieves and maintains tight long-term control.
La insulinoterapia es un arte y actualmente contamos con nuevas formulaciones y otras en proceso de investigación y aprobación. Ponencia presentada en las jornadas del benemérito H2M.
The document discusses recent developments in type 2 diabetes mellitus (T2DM). It covers topics like the increasing prevalence of T2DM globally, changes in pathogenesis understanding with recognition of incretin deficiency as the third defect, use of HbA1c for diagnosis, and treatment algorithms targeting both fasting and post-prandial glucose. Newer treatment options discussed include dipeptidyl peptidase-4 inhibitors, newer glucagon-like peptide-1 receptor agonists with different profiles, ultra long-acting basal insulin degludec, sodium-glucose cotransporter 2 inhibitors, glucokinase activators, and GPR40 modulators. Stem cell therapy is also mentioned as a novel approach
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.
The document discusses the role of DPP-4 inhibition and sitagliptin in the management of type 2 diabetes. It provides evidence that sitagliptin increases active GLP-1 and GIP levels, resulting in improved glycemic control through increased insulin secretion, decreased glucagon levels, and reduced glucose levels. Studies show sitagliptin to be an effective monotherapy and when added to other oral medications, with benefits seen within days and a generally well-tolerated safety profile compared to sulfonylureas.
This document discusses clinical implications for preventing and treating type 2 diabetes by promoting beta-cell function. Short-term therapies like insulin or sulfonylureas can improve beta-cell secretion in the short-term. Long-term, lifestyle interventions like weight loss and exercise are effective at improving insulin sensitivity and stabilizing beta-cell function. Clinical trials also show that medications like metformin, acarbose, orlistat, and troglitazone can reduce diabetes risk by 25-58% by preserving beta-cell function.
Are you Struggling to Control of your Diabetes and Weight?
People who are overweight or obese are more prone to developing Type 2 diabetes. Those who have Type 1 and Type 2 diabetes with weight problems struggle to control their blood sugar levels. Research shows that people with diabetes find it more difficult to lose weight than those without diabetes.
Weight loss significantly improves blood sugar control and also reduces the risk of getting complications from diabetes. However, whilst attempting to lose weight, people with diabetes find it hard to restrict their intake of food since eating less may trigger hypoglycaemia (low blood sugar). All these facts explain the need for specialist input in management of weight in people with diabetes.
This Slideshow gives you insight to Diabesity
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/
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.
Individuals with type 2 diabetes must change their eating patterns and meal plan according to nutrition recommendations. Along with carbohydrates, the amount of protein and fat consumed is important for maintaining good metabolic control, weight management, and preventing long-term complications. The ADA recommends that individuals with type 2 diabetes consume 15-20% of calories from protein and limit saturated and trans fats. Recent research shows that regularly snacking on high-protein foods as part of a habitual diet can help with fat loss without significantly impacting health biomarkers.
Slide Presentation
Diabetes Melliuts Type 2 management basics are life style modifications followed by use of Metformin
What is the best and safest next pharmacologic choice
The document discusses sitagliptin, a novel dipeptidyl peptidase-4 (DPP-4) inhibitor for treating type 2 diabetes. It describes how DPP-4 inhibition increases levels of active incretin hormones GLP-1 and GIP, improving glycemic control. Clinical trials showed sitagliptin is a potent, selective, and reversible DPP-4 inhibitor. It provides >80% inhibition of DPP-4 with once-daily dosing, increasing active incretin levels and insulin secretion while decreasing glucagon. Sitagliptin treatment was well-tolerated and improved glycemic control in patients with type 2 diabetes.
Combining insulin and GLP-1 receptor agonists like Victoza provides complementary benefits for managing type 2 diabetes. Studies show adding Victoza to basal insulin regimens results in: improved glycemic control as shown by greater reductions in HbA1c levels of around 1%; weight loss or weight neutral effects compared to weight gain with insulin alone; and a low risk of hypoglycemia. The combination helps address insulin's limitations of weight gain and variability in glucose lowering by enhancing insulin's effects and reducing glucagon secretion from Victoza. Overall, combining these therapies provides effective glycemic control while minimizing side effects.
The document discusses emerging therapies for type 2 diabetes that aim to preserve beta-cell function and mass by reducing beta-cell workload. It describes how glucagon-like peptide-1 (GLP-1) and exenatide, a GLP-1 receptor agonist, stimulate insulin secretion, increase beta-cell proliferation, and inhibit apoptosis. Studies show that GLP-1 and exenatide improve glycemic control when added to metformin and/or sulfonylurea therapy in patients with type 2 diabetes. The document concludes that preventing the gradual loss of beta-cell function and mass will be important to treat type 2 diabetes.
This document summarizes a sub-analysis of the Japan EPA Lipid Intervention Study (JELIS) that compared the risk of coronary artery disease (CAD) between patients with impaired glucose metabolism (IGM) and normoglycemic (NG) patients, and assessed the effect of eicosapentaenoic acid (EPA) on CAD incidence in IGM patients. The analysis found that IGM patients had a significantly higher risk of CAD compared to NG patients. Treatment with EPA resulted in a 22% decrease in CAD incidence in IGM patients and an 18% decrease in NG patients, although the decrease was only statistically significant for IGM patients.
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 provides an overview of canagliflozin, an SGLT2 inhibitor used to treat type 2 diabetes. It discusses the pathogenesis of type 2 diabetes, progressive beta cell dysfunction, and the kidney's role in glucose regulation. It then reviews canagliflozin's mechanism of action as an SGLT2 inhibitor, increasing urinary glucose excretion and reducing blood glucose levels. The document summarizes canagliflozin's clinical trials, pharmacokinetics, efficacy, safety profile, and effects on renal function and lipids.
Our aim is to reduce morbidity and mortality related to Non communicable diseases such as hypertension, diabetes, cardiovascular disease, stroke, Obesity, Cancer and lifestyle diseases among those least able to withstand the burden of the disease.
Modern therapy in diabetics with cad scintic dayOsama Almaraghi
This document provides information on modern therapy for diabetics with coronary artery disease. It discusses the following key points in 3 sentences:
Diabetes is a global epidemic that is increasing worldwide. Cardiovascular disease is the leading cause of death for diabetics, as they face comparable heart attack risks to those with a previous heart attack. The document reviews guidelines for glycemic, blood pressure, and lipid control to reduce cardiovascular risks and discusses various drug therapy options for treating diabetes in patients with cardiovascular disease.
Achieving Treatment Outcome With DPP4i for Diabetic Patient "Efficacy Beyond ...Suharti Wairagya
This document provides an overview of achieving treatment outcomes for diabetic patients using DPP4 inhibitors. It begins with background on the presenter and discusses prevalence of diabetes worldwide. It then covers updates on diabetes classification, diagnosis, and management approaches from ADA guidelines. It discusses antihyperglycemic therapy and PERKENI guidelines. The document focuses on incretins and DPP-4 inhibition, comparing different DPP4 inhibitors. Studies show vildagliptin provides better 24-hour glucose fluctuation control and reduction in oxidative stress compared to sitagliptin. The conclusion is that vildagliptin may be better than sitagliptin at reducing glycemic variability and its associated complications.
1) Current diabetes treatments often fail to achieve glycemic targets over time and treatment related issues like weight gain and hypoglycemia can decrease tight glycemic control.
2) HbA1c alone does not provide a full picture of glycemic fluctuations and both fasting and post-prandial glucose need to be addressed.
3) A more comprehensive approach is needed to glycemic management that minimizes weight gain and hypoglycemia and achieves and maintains tight long-term control.
La insulinoterapia es un arte y actualmente contamos con nuevas formulaciones y otras en proceso de investigación y aprobación. Ponencia presentada en las jornadas del benemérito H2M.
The document discusses recent developments in type 2 diabetes mellitus (T2DM). It covers topics like the increasing prevalence of T2DM globally, changes in pathogenesis understanding with recognition of incretin deficiency as the third defect, use of HbA1c for diagnosis, and treatment algorithms targeting both fasting and post-prandial glucose. Newer treatment options discussed include dipeptidyl peptidase-4 inhibitors, newer glucagon-like peptide-1 receptor agonists with different profiles, ultra long-acting basal insulin degludec, sodium-glucose cotransporter 2 inhibitors, glucokinase activators, and GPR40 modulators. Stem cell therapy is also mentioned as a novel approach
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.
The document discusses the role of DPP-4 inhibition and sitagliptin in the management of type 2 diabetes. It provides evidence that sitagliptin increases active GLP-1 and GIP levels, resulting in improved glycemic control through increased insulin secretion, decreased glucagon levels, and reduced glucose levels. Studies show sitagliptin to be an effective monotherapy and when added to other oral medications, with benefits seen within days and a generally well-tolerated safety profile compared to sulfonylureas.
This document discusses clinical implications for preventing and treating type 2 diabetes by promoting beta-cell function. Short-term therapies like insulin or sulfonylureas can improve beta-cell secretion in the short-term. Long-term, lifestyle interventions like weight loss and exercise are effective at improving insulin sensitivity and stabilizing beta-cell function. Clinical trials also show that medications like metformin, acarbose, orlistat, and troglitazone can reduce diabetes risk by 25-58% by preserving beta-cell function.
Are you Struggling to Control of your Diabetes and Weight?
People who are overweight or obese are more prone to developing Type 2 diabetes. Those who have Type 1 and Type 2 diabetes with weight problems struggle to control their blood sugar levels. Research shows that people with diabetes find it more difficult to lose weight than those without diabetes.
Weight loss significantly improves blood sugar control and also reduces the risk of getting complications from diabetes. However, whilst attempting to lose weight, people with diabetes find it hard to restrict their intake of food since eating less may trigger hypoglycaemia (low blood sugar). All these facts explain the need for specialist input in management of weight in people with diabetes.
This Slideshow gives you insight to Diabesity
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/
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.
Individuals with type 2 diabetes must change their eating patterns and meal plan according to nutrition recommendations. Along with carbohydrates, the amount of protein and fat consumed is important for maintaining good metabolic control, weight management, and preventing long-term complications. The ADA recommends that individuals with type 2 diabetes consume 15-20% of calories from protein and limit saturated and trans fats. Recent research shows that regularly snacking on high-protein foods as part of a habitual diet can help with fat loss without significantly impacting health biomarkers.
Slide Presentation
Diabetes Melliuts Type 2 management basics are life style modifications followed by use of Metformin
What is the best and safest next pharmacologic choice
The document discusses sitagliptin, a novel dipeptidyl peptidase-4 (DPP-4) inhibitor for treating type 2 diabetes. It describes how DPP-4 inhibition increases levels of active incretin hormones GLP-1 and GIP, improving glycemic control. Clinical trials showed sitagliptin is a potent, selective, and reversible DPP-4 inhibitor. It provides >80% inhibition of DPP-4 with once-daily dosing, increasing active incretin levels and insulin secretion while decreasing glucagon. Sitagliptin treatment was well-tolerated and improved glycemic control in patients with type 2 diabetes.
Combining insulin and GLP-1 receptor agonists like Victoza provides complementary benefits for managing type 2 diabetes. Studies show adding Victoza to basal insulin regimens results in: improved glycemic control as shown by greater reductions in HbA1c levels of around 1%; weight loss or weight neutral effects compared to weight gain with insulin alone; and a low risk of hypoglycemia. The combination helps address insulin's limitations of weight gain and variability in glucose lowering by enhancing insulin's effects and reducing glucagon secretion from Victoza. Overall, combining these therapies provides effective glycemic control while minimizing side effects.
The document discusses emerging therapies for type 2 diabetes that aim to preserve beta-cell function and mass by reducing beta-cell workload. It describes how glucagon-like peptide-1 (GLP-1) and exenatide, a GLP-1 receptor agonist, stimulate insulin secretion, increase beta-cell proliferation, and inhibit apoptosis. Studies show that GLP-1 and exenatide improve glycemic control when added to metformin and/or sulfonylurea therapy in patients with type 2 diabetes. The document concludes that preventing the gradual loss of beta-cell function and mass will be important to treat type 2 diabetes.
This document summarizes a sub-analysis of the Japan EPA Lipid Intervention Study (JELIS) that compared the risk of coronary artery disease (CAD) between patients with impaired glucose metabolism (IGM) and normoglycemic (NG) patients, and assessed the effect of eicosapentaenoic acid (EPA) on CAD incidence in IGM patients. The analysis found that IGM patients had a significantly higher risk of CAD compared to NG patients. Treatment with EPA resulted in a 22% decrease in CAD incidence in IGM patients and an 18% decrease in NG patients, although the decrease was only statistically significant for IGM patients.
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 provides an overview of canagliflozin, an SGLT2 inhibitor used to treat type 2 diabetes. It discusses the pathogenesis of type 2 diabetes, progressive beta cell dysfunction, and the kidney's role in glucose regulation. It then reviews canagliflozin's mechanism of action as an SGLT2 inhibitor, increasing urinary glucose excretion and reducing blood glucose levels. The document summarizes canagliflozin's clinical trials, pharmacokinetics, efficacy, safety profile, and effects on renal function and lipids.
Our aim is to reduce morbidity and mortality related to Non communicable diseases such as hypertension, diabetes, cardiovascular disease, stroke, Obesity, Cancer and lifestyle diseases among those least able to withstand the burden of the disease.
Modern therapy in diabetics with cad scintic dayOsama Almaraghi
This document provides information on modern therapy for diabetics with coronary artery disease. It discusses the following key points in 3 sentences:
Diabetes is a global epidemic that is increasing worldwide. Cardiovascular disease is the leading cause of death for diabetics, as they face comparable heart attack risks to those with a previous heart attack. The document reviews guidelines for glycemic, blood pressure, and lipid control to reduce cardiovascular risks and discusses various drug therapy options for treating diabetes in patients with cardiovascular disease.
Achieving Treatment Outcome With DPP4i for Diabetic Patient "Efficacy Beyond ...Suharti Wairagya
This document provides an overview of achieving treatment outcomes for diabetic patients using DPP4 inhibitors. It begins with background on the presenter and discusses prevalence of diabetes worldwide. It then covers updates on diabetes classification, diagnosis, and management approaches from ADA guidelines. It discusses antihyperglycemic therapy and PERKENI guidelines. The document focuses on incretins and DPP-4 inhibition, comparing different DPP4 inhibitors. Studies show vildagliptin provides better 24-hour glucose fluctuation control and reduction in oxidative stress compared to sitagliptin. The conclusion is that vildagliptin may be better than sitagliptin at reducing glycemic variability and its associated complications.
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Basal-Insulin-CME_Slides (2).pptx
1.
2. Learning Objectives
• Describe unmet needs of patients with type 2 diabetes
• Outline the role of basal insulin and GLP-1RAs as described in current
guidelines
• Compare the benefits and limitations of GLP-1RA vs prandial insulin as add-on
to basal insulin
• Describe the glycemic and non-glycemic outcomes observed with fixed-ratio
basal insulin/GLP-1RA combination products
• Initiate and titrate fixed-ratio basal insulin/GLP-1RA combination products
3. Case Scenario #1
61-year-old man diagnosed with type 2 diabetes mellitus 3 months ago (A1c 8.7%)
Weight: 187 lb
BMI: 28.8 kg/m2
BP: 126/78 mm Hg
A1c: 7.6%
FPG: 128 mg/dL
PPG: 196 mg/dL
eGFR: 92 mL/min/1.73 m2
Vital Signs and
Laboratory Results
• Lifestyle management
• Metformin 1000 mg BID
Current
Management
Has had some success in
modifying diet and increasing
physical activity
Notes
4. Diabetes Mellitus as a Cardiovascular Risk Factor
Kannel WB, et al. JAMA. 1979;241:2035-2038.
0 5 10 15 20 25 30 35 40 45
Coronary Heart Disease
Atherothrombotic Brain Infarction
Intermittent Claudication
Congestive Heart Failure
Cardiovascular Death
Cardiovascular Disease
Annual age-adjusted event rate per 1000 patient-years
Framingham Heart Study
Men with Diabetes Men without Diabetes Women with Diabetes Women without Diabetes
6. Prevalence of Persons with Diabetes Achieving
Cardiovascular Targets: NHANES 2011-2014
Sun X, et al. BMC Public Health. 2017;17:893.
78.8%
67.0%
56.8% 55.8%
76.7%
77.2%
67.3%
57.3% 56.0%
78.4%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Achieving A1c <7.0% Achieving BP <130/80 mmHg Achieving LDL-C <100 mg/dL
Percent
of
Survey
Respondents
Women w/o Diabetes Women w/Diabetes Men w/o Diabetes Men w/Diabetes
7. The Disconnect Between Clinical Trial and
Real-world Results
1. Pratley RE, et al. Lancet. 2010;375:1447-1456. 2. Singhal M, et al. ISPOR Annual International Meeting. May 16-20, 2015; Poster PDB10.
3. Garber A, et al. Lancet. 2009;373:473-481.
†Quintiles EMR database, N=1474 patients with T2D who were prescribed liraglutide or exenatide once weekly.
–1.2%
–1.5%
–0.9%
CLINICAL TRIALS
REAL WORLD†
–0.8%
–1.1%
–0.7%
0
–1.2
–0.4
–0.8
–0.2
Change
in
A1c
(%)
–1.0
–0.6
–1.4
–1.6
1.2 mg 1.8 mg
N=251 N=247
8.3%
Liraglutide3
N=225
Reduction in A1c
(6 Months)
1.2 mg 1.8 mg
GLP-1 RAs in the REAL WORLD2†
N=221
8.4%
Liraglutide1
N=1474
8.6%
N=902
8.6%
Baseline A1c
Reduction in A1c
(12 Months)
8. Patient Adherence with Medications for T2DM
Is Suboptimal
Farr AM, et al. Adv Ther. 2014;31(12):1287-1305. Zhou FL, et al. Diabetes Obes Metab. 2018;20:1298-1301.
Adherence defined as: SU, TZD, DPP-4i: patients who maintained proportion of days covered ≥0.80 over 1 year
Basal insulin: patients with refill gap ≤90 days over 18 months
41%
37%
47%
43%
0%
20%
40%
60%
80%
100%
Sulfonylurea (n=134,961) Thiazolidinedione (n=42,012) Dipeptidyl peptidase-4
inhibitor (n=61,399)
Basal Insulin (N=3993)
Percent
Adherent
9. Depression and Distress are Common in
Patients with Diabetes
• Meta-analysis of 39 studies (N=20,218) showed1
Odds of depression doubled (2x) in diabetes group
Point prevalence: women 28%; men 18%
• In T2DM, depression is more common in those
Treated with insulin vs lifestyle or OADs2
Who experience recurrent hypoglycemia and poor glycemic control3
With diabetes distress4
1.Anderson RJ, et al. Diabetes Care. 2001;24:1069-1078.
2.Hermanns N, et al. Diabet Med. 2005;22(3):293-300
3.Holt RIG, et al. Curr Diabetes Rep. 2014;14(6):491.
4.Perrin NE, et al. Diabet Med. 2017;34:1508-1520.
10. Strategies to Identify and Address
Patient Concerns
• Active listening
• Motivational interviewing
• Ask open-ended questions
• Involve patient in decision-making process
11. Resources for Patient Education
• American Diabetes Association
http://www.diabetes.org/diabetes-basics/type-2/?loc=util-header_type2
• American Association of Clinical Endocrinologists
http://outpatient.aace.com/
• National Diabetes Education Program
https://www.niddk.nih.gov/health-information/professionals/clinical-tools-
patient-education-outreach?cs=ndep
12. Case Scenario #2
53-year-old woman newly diagnosed with type 2 diabetes mellitus
Weight: 198 lb
BMI: 32.9 kg/m2
BP: 132/86 mm Hg
A1c: 8.4%
FPG: 156 mg/dL
eGFR: 84 mL/min/1.73 m2
Vital Signs and
Laboratory Results
• Lifestyle management in
consultation with dietitian
• Atorvastatin 40 mg/d
• Ramipril 10 mg/d
• NTG 0.3 mg SL prn
• Aspirin 81 mg/d
Current
Management
• PMH: hyperlipidemia, angina,
obesity
• She is upset with being
diagnosed with ‘yet another
disease’
• Adherence with current
treatment has been
challenging
Notes
16. Characteristics of Key Medications for
Type 2 Diabetes Mellitus
Bolen S, et al. https://www.effectivehealthcare.ahrq.gov/ehc/products/607/2215/diabetes-update-2016-report.pdf
American Diabetes Association. Diabetes Care. 2018;41(Suppl 1):S73-S85.
Garber AJ, et al. Endocr Pract. 2018;24:91-120.
†When added to metformin
↑, decrease; ↔, no change; ↓, increase
Magnitude of
A1c Lowering†
Adverse Events Risk of
Hypoglycemia
Weight
Effect
Cost
DPP-4i 0.4% to 0.5% Rare Low High
GLP-1RA 0.5% to 1.3% GI Low High
Insulin
(basal analog)
Theoretically
unlimited
Hypoglycemia
High High
SGLT-2i 0.5% to 1% GU, dehydration,
fracture
Low High
Sulfonylurea 1% Hypoglycemia Moderate Low
TZD 0.4% to 0.9% Edema, HF, fracture Low Low
17. GLP-1 Receptor Agonists: Benefits
• Low risk of hypoglycemia
• Increase insulin secretion in a glucose-dependent manner
• Improvements in cardiovascular markers
Blood pressure, triglycerides, low-density lipoprotein cholesterol
• Use as an alternative to metformin
• Promote modest weight loss
Balena R, et al. Diabetes Obes Metab. 2013;15:485-502.
18. Cardiovascular Safety and Benefit for
GLP-1 RAs in Patients With T2DM
1.Holman R, et al. N Engl J Med. 2017;377(13):1228-1239.
2.Marso SP, et al. N Engl J Med. 2016;375(4):311-322.
3.Pfeffer MA, et al. N Engl J Med. 2015;373(23):2247-2257.
4.Marso SP, et al. N Engl J Med. 2016;375(19):1834-1844.
CV, cardiovascular; F/U, follow-up; MI, myocardial infarction; UA, unstable angina.
a Composite of CV death, nonfatal MI, nonfatal stroke
b Composite of CV death, nonfatal MI, nonfatal stroke, hospitalization for UA
c Composite of CV death, nonfatal MI, nonfatal ischemic stroke
GLP-1 Receoptor Agonist Primary endpoint
Heart failure
hospitalization
All-cause death
Exenatide1
(N=14,752; 3.2 y median F/U)
0.91a
(0.83-1.00)
0.94
(0.78-1.13)
0.86
(0.77-0.97)
Liraglutide2
(N=9340; 3.8 y median F/U)
0.87a
(0.78-0.97)
0.87
(0.73-1.05)
0.85
(0.74-0.97)
Lixisenatide3
(N=6068; 2.1 median F/U)
1.02b
(0.89-1.17)
0.96
(0.75-1.23)
0.94
(0.78-1.13)
Semaglutide4
(N=3297; 2.1 y median F/U)
0.74c
(0.58-0.95)
1.11
(0.77-1.61)
1.05
(0.74-1.50)
19. Cardiovascular Safety and Benefit for
SGLT-2is in Patients With T2DM
1.Neal B, et al. N Engl J Med. 2017;377(7):644-657.
2.Zinman B, et al. N Engl J Med. 2015;373(22):2117-2128.
CV, cardiovascular; F/U, follow-up; MI, myocardial infarction.
†Composite of CV death, nonfatal MI, nonfatal stroke
SGLT-2 Inhibitor
Primary
endpoint
Heart failure
hospitalization
All-cause death
Canagliflozin1
(N=10,142; 2.4 y median F/U)
0.86†
(0.75-0.97)
0.67
(0.52-0.87)
0.87
(0.74-1.01)
Empagliflozin2
(N=7020; 3.1 median F/U)
0.86†
(0.74-0.99)
0.65
(0.50-0.85)
0.68
(0.57-0.82)
20. Cardiovascular Safety of Basal Insulin
1.ORIGIN Investigators. N Engl J Med. 2012;367(4):319-328.
2.Marso SP, et al. N Engl J Med. 2017;377(8):723-732.
Nonfatal Myocardial Infarction, Nonfatal Stroke, Death From Cardiovascular Causes
ORIGIN Trial DEVOTE Trial
21. Case Scenario #3
64-year-old woman with type 2 diabetes mellitus for 7 years
Weight: 204 lb
BMI: 33.6 kg/m2
BP: 136/82 mm Hg
A1c: 8.2%
FPG: 118 mg/dL
PPG: 218 mg/dL
LDL-C: 86 mg/dL
Triglycerides: 160 mg/dL
eGFR: 60 mL/min/1.73 m2
Vital Signs and
Laboratory Results
• Lifestyle management
• Metformin 1000 mg BID
• Insulin detemir 68 units (0.73
units/kg) at bedtime
• HCTZ 25 mg/d
• Lisinopril 20 mg/d
• Atorvastatin 40 mg/d
Current
Management
• PMH: hypertension, dyslipidemia,
obesity
• A1c 13 mos ago: 7.2%
• Has experienced several episodes
of symptomatic hypoglycemia over
past few months
• Episode early yesterday
morning required treatment in
emergency department
(blood glucose 52 mg/dL)
Notes
22. Uptitrating Basal Insulin May Not Achieve A1c Target
and May Increase Risk of Hypoglycemia
Reid T, et al. Int J Clin Pract. 2016;70:56–65.
-1.61 -1.59 -1.57
-1.49
-1.43
-1.26
-1.8
-1.6
-1.4
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
0.5 IU/kg 0.7 IU/kg 1.0 IU/kg
A1c
change
from
baseline
(%)
At or below cut-off Exceeding cut-off
1.55
1.12
0.71
4.49
3.90
2.85
0.00
0.50
1.00
1.50
2.00
2.50
3.00
3.50
4.00
4.50
5.00
0.5 IU/kg 0.7 IU/kg Dose
cut-off
1.0 IU/kg
Overall
hypoglycemia
event
rate
(events
per
patient-year)
Prior to exceeding cut off dose After exceeding cut-off
Pooled analysis of glycemic profiles from 15 treat-to-target trials
in which insulin-naïve T2DM patients were treated with insulin glargine and OADs for ≥24 weeks (N=2837)
23. Combination of Basal Insulin with a GLP-1 RA
Has a Scientific Basis
Little S, et al. Diabetes Technol Ther. 2011:13(suppl 1):S53-S64.
Cohen ND, et al. Med J Aust. 2013;199(4):246-249.
Carris NW, et al. Drugs. 2014;74(18):2141-2152.
Basal insulin analogs†
• Control nocturnal and FPG
• Simple to initiate
• Achieve A1c targets in ~50-60%
• Hypoglycemia remains a concern
• Modest weight increase (1 to 3 kg)
GLP-1 RAs
• Pronounced PPG control
(especially short-acting agents)
• Simple to initiate
• Achieve A1c targets in ~40-60%
• Low risk of hypoglycemia
• Weight lowering/neutral effects
Complementary
actions
Additive
actions
†Note: NPH insulin is an alternative for use in combination with a GLP-1RA but has not been studied
24.
25. Adding a GLP-1 RA vs Prandial Insulin† to
Basal Insulin– Systematic Review
Maiorino MI, et al. Diabetes Care. 2017;40(4):614-624.
†Results reported from 2 basal-plus and 7 basal-bolus studies including at least 60 patients/arm with T2DM
-0.11%
P=0.031
-4.1 kg
P<0.001
-5
-4
-3
-2
-1
0
1
2
Favors
Basal
Insulin
+
GLP-1RA
Favors
Basal
Insulin
+
Prandial
Insulin
Change
in Weight
Change
in A1c
1.09
P=0.076
0.68
P=0.005
-1
-0.5
0
0.5
1
1.5
A1C ≤7% Risk of Hypoglycemia
Favors
Basal
Insulin
+
GLP-1RA
Favors
Basal
Insulin
+
Prandial
Insulin
Weighted Mean
Difference vs Placebo
Relative Risk
26. Adding a GLP-1 RA to Basal Insulin Is Equally
Effective Compared to Adding Prandial Insulin
Diamant M, et al. Diabetes Care. 2014;37:2763-2773. Balena R, et al. Diab Obes Metab. 2013;15:485-502.
Carris NW, et al. Drugs. 2014;74(18):2141-2152. Holst JJ, Vilsbøll T. Diabetes Obes Metab. 2013;15(1):3-14.
Vora J, et al. Diabetes Care. 2013;36(suppl 2):s226-S232.
• Fewer injections
• Improved adherence?
• Less glucose monitoring required
• Lower insulin dose
• Weight benefit
• Less hypoglycemia
• More (GI) side effects
• Cost/Affordability
And… But…
27. Case Scenario #4
69-year-old man with type 2 diabetes for 12 years
Weight: 187 lb
BMI: 29.5 kg/m2
BP: 128/84 mm Hg
A1c: 6.9%
FPG: 106 mg/dL
PPG: 176 mg/dL
LDL-C: 68 mg/dL
Triglycerides: 126 mg/dL
eGFR: 56 mL/min/1.73 m2
Vital Signs and
Laboratory Results
• Lifestyle management
• Metformin 1000 mg BID
• Insulin glargine 46 units (0.54
units/kg) at bedtime
• Exenatide 10 mcg BID
• HCTZ 25 mg/d
• Valsartan 320 mg/d
• Pravastatin 40 mg/d
• Aspirin 81 mg/d
Current
Management
• Treatment has been modified
through the years to maintain
A1c 7%
• PMH: hypertension,
dyslipidemia, myocardial
infarction (3 years ago)
• Has found it increasingly difficult
to adhere to treatment; exhibiting
distress
Notes
28. Rationale for Co-Formulation of Basal Insulin/GLP-1RA:
Barriers to Concomitant Use of Individual Products
• More injections clinical inertia
Decreased adherence
Reduced satisfaction
Compromised self-management
• Uncertainty of choosing starting dose, adding therapies, titration
of each drug
Peyrot M, et al. Diabet Med. 2012;29(5):682-689. Peyrot M, et al. Diabetes Care. 2010;33(2):240-245.
29. Rationale for Co-Formulation of Basal
Insulin/GLP-1RA: Benefits
• Provides pathophysiologic-based treatment
• Targets both fasting and postprandial glucose
• Single injection
May reduce out-of-pocket cost
• Safe, effective initiation and titration algorithm
• Avoids uncertainty regarding titrating individual components
• Minimizes delays in achieving glycemic control
30. Insulin Degludec/Liraglutide
(Xultophy® 100/3.6)
Insulin Glargine/Lixisenatide
(Soliqua 100/33)
Administration Subcutaneous Subcutaneous
Dose timing Once daily at same time each day
with/without food
Once daily within the hour prior to the first
meal of the day
Maximum daily dose 50 units degludec, 1.8 mg liraglutide 60 units glargine, 20 mcg lixisenatide
Dosing Based on degludec Based on glargine
Fixed-Ratio Basal Insulin/GLP-1 RA
Combinations
XULTOPHY® 100/3.6 (insulin degludec and liraglutide injection). Prescribing Information, Novo Nordisk. November 2016.
SOLIQUA™ 100/33 (insulin glargine and lixisenatide injection) [package insert]. Sanofi-Aventis U.S.; March 2018.
31. Fasting Plasma Glucose (mg/dL)
A1c
IDegLira in Insulin-Naïve Patients with T2DM not
Controlled on OADs: DUAL I
Gough SCL, et al. Diabetes Obes Metab. 2015;17:965-973.
FPG, fasting plasma glucose; A1c, glycated hemoglobin; OADs, metformin ±pioglitazone; LIRA, liraglutide; IDeg, insulin degludec; IDegLira, fixed-ratio
insulin degludec/liraglutide.
32. Change in A1c by Baseline BMI
IDegLira in Insulin-Naïve Patients with T2DM not
Controlled on OADs: DUAL I (cont)
Gough SCL, et al. Diabetes Obes Metab. 2015;17:965-973.
% of Patients Achieving A1c Targets
33. IDegLira in Insulin-Naïve Patients with T2DM not
Controlled on OADs: DUAL I (cont)
Gough SCL, et al. Diabetes Obes Metab. 2015;17:965-973.
Change in Body Weight
Daily Insulin Dose
34. IDegLira in Insulin-Naïve Patients with T2DM not
Controlled on OADs: DUAL I (cont)
Gough SCL, et al. Diabetes Obes Metab. 2015;17:965-973.
% of Patients with Nausea
35. IDegLira in Patients with T2DM Not Controlled
on Basal Insulin†: DUAL II
Buse JB, et al. Diabetes Care. 2014;37:2926-2933.
†Patients withT2DM not controlled on basal insulin + metformin ± SU or glinides
Time (weeks)
A1c
(%)
9.5
0
8.5
7.5
10 22
12 26
6.5
IDegLira (N=199) IDeg (N=199)
∆ = -1.05%,
p<0.0001
9.0
8.0
7.0
0 4 16
8 20
2 14
6 18 24
A1c
Mean final basal insulin dose/day: IDegLira, 45 units; degludec 45 units
-50
-10
Mean
Change
from
Baseline
in
FPG
(mg/dL)
-70
-30
0
-46.4
-60
P=0.0019
-40
-20
-62.4
Change in Fasting Plasma Glucose
36. IDegLira in Patients with T2DM Not Controlled on
GLP-1RA + OAD†: DUAL III
Linjawi S, et al. Diabetes Ther. 2017;8:101-114.
†Maximum-dose exenatide twice daily or liraglutide once daily plus metformin ± pioglitazone ± sulfonylurea
A1c (%)
37. Plasma Glucose
Fasting Plasma Glucose
IDegLira in Patients with T2DM Not Controlled on
GLP-1RA + OAD†: DUAL III (cont)
Linjawi S, et al. Diabetes Ther. 2017;8:101-114.
†Maximum-dose exenatide twice daily or liraglutide once daily plus metformin ± pioglitazone ± sulfonylurea
38. Change in A1c by
Baseline A1c
Change in A1c by
Baseline Fasting Plasma
Change in A1c by
Baseline Body Mass Index
IDegLira in Patients with T2DM Not Controlled on
Insulin Glargine + OAD†: DUAL V
Lingvay I, et al. Diabetes Obes Metab. 2018;20:200-205.
†Insulin glargine + metformin
39. IDegLira in Patients with T2DM Not Controlled on
Insulin Glargine + OAD†: DUAL VII (cont)
Billings LK, et al. Diabetes Care. 2018;41:1009-1016.
†Insulin glargine + metformin
40. IDegLira: Other Safety Events†
1. Gough SCL, et al. Diabetes Obes Metab. 2015;17:965-973. 2. Buse JB, et al. Diabetes Care. 2014;37:2926-2933. 3. Linjawi S, et al.
Diabetes Ther. 2017;8:101-114. 4. Lingvay I, et al. JAMA. 2016;315:898-907. 5. Billings LK, et al. Diabetes Care. 2018;41:1009-1016.
†Positively adjudicated by a blinded monitoring committee and judged by the investigator as treatment-related
DEG, insulin degludec; GLAR, insulin glargine; IDegLira, fixed-ratio insulin degludec/liraglutide; LIRA, liraglutide; NR, not reported.
DUAL I1 DUAL II2 DUAL III3 DUAL V4 DUAL VII5
Major adverse
CV event
IDegLira 4/833
DEG 1/413
LIRA 1/414
IDegLira 1/199
DEG 2/199
IDegLira 2/292
GLP-1RA 0/146
IDegLira 1/278
GLAR 1/279
IDegLira 0/252
GLAR+ASP 0/254
Pancreatitis IDegLira 0/833
DEG 0/413
LIRA 1/414
IDegLira 0/199
DEG 0/199
IDegLira 0/292
GLP-1RA 0/146
IDegLira 0/278
GLAR 0/279
IDegLira 0/252
GLAR+ASP 0/254
Pancreatic
cancer
NR IDegLira 0/199
DEG 1/199
NR IDegLira 0/278
GLAR 0/279
IDegLira 0/252
GLAR+ASP 0/254
Medullary
thyroid cancer
IDegLira 0/833
DEG 0/413
LIRA 0/414
IDegLira 0/199
DEG 0/199
IDegLira 0/292
GLP-1RA 0/146
IDegLira 0/278
GLAR 0/279
IDegLira 0/252
GLAR+ASP 0/254
41. IGlarLixi in Insulin-Naïve Patients with T2DM:
LixiLan-O
Patients with T2DM not controlled on Metformin ± second OAD
Rosenstock J, et al. Diabetes Care. 2016;39:2026-2035.
†P<0.05. ‡P<0.0001.
iGlarLixi, fixed-ratio insulin glargine/lixisenatide; OAD, oral antidiabetic agent.
Mean
A1c
(%)
8.5
6.5
6.0
8.0
7.5
8
Baseline
24
12 30
Week
7.0
Screening
iGlarLixi (N = 469)
Mean
Difference
P-value
vs Lixi (N = 234) -0.78% <0.0001
vs Glargine (N = 467) -0.29% <0.0001
Lixi Glargine iGlarLixi
6.5%
iGlarLixi Glargine Lixi
6.8%
7.3%
8.1%
8.2%
42. IGlarLixi in Insulin-Naïve Patients with T2DM:
LixiLan-O (cont)
Rosenstock J, et al. Diabetes Care. 2016;39:2026-2035.
†PPG changes are mean for all 3 meals.
Patients with T2DM not controlled on Metformin ± second OAD
FPG
-60
-20
Mean
Change
from
Baseline
(mg/dL)
-80
-40
0
2-h PPG Excursions†
-27.0
P<0.0001
-60
-20
-80
-40
0
-58.1
P<0.0001
iGlarLixi (N = 468) Glargine (N = 466) Lixi (N = 233)
-59.0
-62.4
-3.2
-41.7
2
-2.3
P<0.0001
1.1
-0.3
1
0
-1
-2
-3
Weight Change (kg)
Mean final basal insulin dose/day: IGlarLixi, 39.8 units; glargine 40.3 units
43. IGlarLixi in Insulin-Naïve Patients with T2DM:
LixiLan-O (cont)
Rosenstock J, et al. Diabetes Care. 2016;39:2026-2035.
iGlarLixi Glargine Lixisenatide
Adverse event leading to discontinuation 2.6% 1.9% 9%
GI adverse event
Nausea
21.7%
9.6%
12.6%
3.6%
36.9%
24.0%
Symptomatic hypoglycemia,
events/patient-year
1.4 1.2 0.3
Cardiovascular event 0.4% 1.5% 0.9%
Allergic reaction 1.3% 0.6% 0.9%
Pancreatitis 0% 0% 0%
Pancreatic cancer 0% 0.2% 0%
44. Efficacy of IGlarLixi in Patients with T2DM Not
Controlled on Basal Insulin: LixiLan-L
Patients with T2DM not controlled on basal insulin + Metformin ± second OAD
Aroda VR, et al. Diabetes Care. 2016;39:1972-1980.
iGlarLixi (N = 366)
Mean
Difference
P-value
vs Glargine (N = 365) -0.52% <0.0001
Mean
A1c
(%)
8.5
6.5
6.0
8.0
7.5
8
Baseline
24
12 30
Week
7.0
Screening
Glargine iGlarLixi
6.9%
7.5%
8.1%
8.5%
iGlarLixi Glargine
(%)
40
10
20
0
60
30
50
% Patients with
A1c < 7.0% at Week 30
55%
30%
Percent
Patients
(%)
40
10
20
0
A1c < 7.0% with No Wt
Gain and No Symptomatic
Hypoglycemia
30
20%
9%
45. Efficacy of IGlarLixi in Patients with T2DM Not Controlled
on Basal Insulin: LixiLan-L (cont)
Aroda VR, et al. Diabetes Care. 2016;39:1972-1980.
†PPG changes are mean for all 3 meals.
Mean final basal insulin dose/day: iGlarLixi, 46.7 units; glargine 46.7 units
iGlarLixi (N = 366)
FPG
-60
-20
Mean
Change
from
Baseline
(mg/dL)
-100
-40
0
-8.3
2-h PPG Excursions†
Glargine (N = 365)
-80
P=NS
-60
-20
-100
-40
0
-8.4
-80
P<0.0001
-70.2
-6.3
-2
0
-1
1 0.7
P<0.0001
-0.7
Weight Change (kg)
46. Safety of IGlarLixi in Patients with T2DM Not Controlled on
Basal Insulin: LixiLan-L
Aroda VR, et al. Diabetes Care. 2016;39:1972-1980.
IGlarLixi Glargine
Adverse event leading to
discontinuation
2.7% 0.8%
GI adverse event
Nausea
17.0%
10.4%
7.9%
0.5%
Symptomatic hypoglycemia,
events/patient-year
3.03 4.22
47. Case Scenario #5
52-year-old woman with T2DM for 7 years and obesity who started basal insulin
1 year ago
Height: 5 ft 4 in
Weight: 187 lb
BMI: 32.1 kg/m2
BP: 127/82 mm Hg
FPG: 149 mg/dL
A1c: 8.0%
eGFR: 75 mL/min/1.73 m2
Vital Signs and
Laboratory Results
• Metformin 1000 mg BID
• Insulin glargine 22 units/d
• Losartan/HCTZ 50/12.5 mg/d
• Simvastatin 20 mg/d
Current
Management
• Adherent to medication and
lifestyle management
• She’s very busy working full time
as a nurse and taking care of her
husband who recently had a stroke
• She says that she feels
overwhelmed
• …and she’s frustrated that she’s
gained 10 lbs since starting insulin
1 year ago
Notes
48. Insulin Degludec/Liraglutide
(Xultophy® 100/3.6)
Insulin Glargine/Lixisenatide
(Soliqua® 100/33)
Dose range delivered per injection 10 to 50 units 15 to 60 units
Prior to initiating Discontinue basal insulin, GLP-1RA
Initial dose 16 units 15 units: if inadequately controlled
with <30 units basal insulin or
lixisenatide
30 units: if inadequately controlled
with 30-60 units basal insulin
Dose timing Once daily at same time each day
with/without food
Once daily within the hour prior to
the first meal of the day
Initiating Fixed-Ratio Basal Insulin/GLP-1 RA
Combinations
XULTOPHY® 100/3.6 (insulin degludec and liraglutide injection). Prescribing Information, Novo Nordisk. November 2016.
SOLIQUA™ 100/33 (insulin glargine and lixisenatide injection) [package insert]. Sanofi-Aventis U.S.; March 2018.
49. Insulin Degludec/Liraglutide
(Xultophy® 100/3.6)
Insulin Glargine/Lixisenatide
(Soliqua® 100/33)
Dosing Based on degludec Based on glargine
Titration Every 3-4 days
Above target: +2 units
Within target: no change
Below target: -2 units
Weekly
Above target: +2 to +4 units
Within target: no change
Below target: -2 to -4 units
Maximum daily dose 50 units degludec,
1.8 mg liraglutide
60 units glargine,
20 mcg lixisenatide
Initiating Fixed-Ratio Basal Insulin/GLP-1 RA
Combinations (cont)
XULTOPHY® 100/3.6 (insulin degludec and liraglutide injection). Prescribing Information, Novo Nordisk. November 2016.
SOLIQUA™ 100/33 (insulin glargine and lixisenatide injection) [package insert]. Sanofi-Aventis U.S.; March 2018.
50. Case Scenario #6
73-year-old man with previously well-controlled type 2 diabetes mellitus whose
adherence has declined over the past year
Weight: 164 lb
BMI: 27.6 kg/m2
BP: 136/92 mm Hg
FPG: 132 mg/dL
PPG: 196 mg/dL
A1c: 7.7%
eGFR: 58 mL/min/1.73 m2
Vital Signs and
Laboratory Results
• Lifestyle management
• Metformin 1000 mg BID
• Insulin detemir 34 units
(0.46 units/kg) at bedtime
• Liraglutide 1.2 mg/d
• HCTZ 12.5 mg/d
• Aspirin 81 mg/d
• Fluticasone nasal spray each
nostril once daily in spring
Current
Management
• PMH: grade 2 retinopathy;
hypertension; seasonal
allergies; mild cognitive
impairment
• Wife diagnosed with stage 3
breast cancer 1 year ago
Notes
51. Insulin Degludec/Liraglutide
(Xultophy® 100/3.6)
Insulin Glargine/Lixisenatide
(Soliqua® 100/33)
Initial dose 16 units 15 units: if inadequately controlled with
<30 units basal insulin or lixisenatide
30 units: if inadequately controlled with
30-60 units basal insulin
Initiating Fixed-Ratio Basal Insulin/GLP-1 RA
Combinations (cont)
XULTOPHY® 100/3.6 (insulin degludec and liraglutide injection). Prescribing Information, Novo Nordisk. November 2016.
SOLIQUA™ 100/33 (insulin glargine and lixisenatide injection) [package insert]. Sanofi-Aventis U.S.; March 2018.
52. Case Scenario #1
61-year-old man diagnosed with type 2 diabetes mellitus 3 months ago (A1c 8.7%)
Weight: 187 lb
BMI: 28.8 kg/m2
BP: 126/78 mm Hg
A1c: 7.6%
FPG: 128 mg/dL
PPG: 196 mg/dL
eGFR: 92 mL/min/1.73 m2
Vital Signs and
Laboratory Results
• Lifestyle management
• Metformin 1000 mg BID
Current
Management
Has had some success in
modifying diet and increasing
physical activity
Notes
53. Case Scenario #2
53-year-old woman newly diagnosed with type 2 diabetes mellitus
Weight: 198 lb
BMI: 32.9 kg/m2
BP: 132/86 mm Hg
A1c: 8.4%
FPG: 156 mg/dL
eGFR: 84 mL/min/1.73 m2
Vital Signs and
Laboratory Results
• Lifestyle management in
consultation with dietitian
• Atorvastatin 40 mg/d
• Ramipril 10 mg/d
• NTG 0.3 mg SL prn
• Aspirin 81 mg/d
Current
Management
• PMH: hyperlipidemia, angina,
obesity
• She is upset with being
diagnosed with ‘yet another
disease’
• Adherence with current
treatment has been
challenging
Notes
54. Case Scenario #3
64-year-old woman with type 2 diabetes mellitus for 7 years
Weight: 204 lb
BMI: 35.6 kg/m2
BP: 136/82 mm Hg
A1c: 8.2%
FPG: 118 mg/dL
PPG: 218 mg/dL
LDL-C: 86 mg/dL
Triglycerides: 160 mg/dL
eGFR: 84 mL/min/1.73 m2
Vital Signs and
Laboratory Results
• Lifestyle management
• Metformin 1000 mg BID
• Insulin detemir 68 units (0.73
units/kg) at bedtime
• HCTZ 25 mg/d
• Atorvastatin 40 mg/d
• Lisinopril 20 mg/d
Current
Management
• PMH: hypertension, dyslipidemia,
obesity
• A1c 13 mos ago: 7.2%
• Has experienced several episodes
of symptomatic hypoglycemia over
past few months
• Episode early yesterday
morning required treatment in
emergency department
(BG 52 mg/dL)
Notes
55. Case Scenario #4
69-year-old man with type 2 diabetes for 12 years
Weight: 187 lb
BMI: 29.5 kg/m2
BP: 128/84 mm Hg
A1c: 6.9%
FPG: 106 mg/dL
PPG: 176 mg/dL
LDL-C: 68 mg/dL
Triglycerides: 126 mg/dL
eGFR: 56 mL/min/1.73 m2
Vital Signs and
Laboratory Results
• Lifestyle management
• Metformin 1000 mg BID
• Insulin glargine 46 units (0.54
units/kg) at bedtime
• Exenatide 10 mcg BID
• HCTZ 25 mg/d
• Valsartan 320 mg/d
• Pravastatin 40 mg/d
• Aspirin 81 mg/d
Current
Management
• Treatment has been modified
through the years to maintain
A1c 7%
• PMH: hypertension,
dyslipidemia, myocardial
infarction (3 years ago)
• Has found it increasingly difficult
to adhere to treatment; exhibiting
distress
Notes
56. Case Scenario #5
52-year-old woman with T2DM for 7 years and obesity who started basal insulin
1 year ago
Height: 5 ft 4 in
Weight: 187 lb
BMI: 32.1 kg/m2
BP: 127/82 mm Hg
FPG: 149 mg/dL
A1c: 8.0%
eGFR: 75 mL/min/1.73 m2
Vital Signs and
Laboratory Results
• Metformin 1000 mg BID
• Insulin glargine 22 units/d
• Losartan/HCTZ 50/12.5 mg/d
• Simvastatin 20 mg/d
Current
Management
• Adherent to medication and
lifestyle management
• She’s very busy working full time
as a nurse and taking care of her
husband who recently had a stroke
• She says that she feels
overwhelmed
• …and she’s frustrated that she’s
gained 10 lbs since starting insulin
1 year ago
Notes
57. Case Scenario #6
73-year-old man with previously well-controlled type 2 diabetes mellitus whose
adherence has declined over the past year
Weight: 164 lb
BMI: 27.6 kg/m2
BP: 136/92 mm Hg
FPG: 132 mg/dL
PPG: 196 mg/dL
A1c: 7.7%
eGFR: 58 mL/min/1.73 m2
Vital Signs and
Laboratory Results
• Lifestyle management
• Metformin 1000 mg BID
• Insulin detemir 34 units
(0.46 units/kg) at bedtime
• Liraglutide 1.2 mg/d
• HCTZ 12.5 mg/d
• Aspirin 81 mg/d
• Fluticasone nasal spray each
nostril once daily in spring
Current
Management
• PMH: grade 2 retinopathy;
hypertension; seasonal
allergies; mild cognitive
impairment
• Wife diagnosed with stage 3
breast cancer 1 year ago
Notes