scholarly journals Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults with Overweight or Obesity and Type 2 Diabetes Mellitus: A 54-Week Randomized Phase 2b Study

2021 ◽  
Author(s):  
Rajaa Nahra ◽  
Tao Wang ◽  
Kishore M. Gadde ◽  
Jan Oscarsson ◽  
Michael Stumvoll ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Body Weight ◽  
Ad Hoc ◽  
Open Label ◽  
Double Blind ◽  
Glucagon Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Design And Methods

<a><b>Objective: </b></a>Cotadutide, a <a>dual GLP-1 and glucagon receptor agonist</a>, is under development for nonalcoholic steatohepatitis (NASH) and type 2 diabetes. The effects of cotadutide on hepatic and metabolic parameters were evaluated in participants with overweight/obesity and type 2 diabetes. <p><b>Research Design and Methods:</b> In this phase 2b study, 834 adults with BMI ≥25kg/m<sup>2</sup> and type 2 diabetes inadequately controlled with metformin (glycated hemoglobin A1c [HbA1c] of 7.0%─10.5% [53─91 mmol/mol]) were randomized to double-blind cotadutide 100µg (n=100), 200µg (n=256), or 300µg (n=256), placebo (n=110), or open-label liraglutide 1.8mg (n=110), all administered subcutaneously (NCT03235050). Coprimary endpoints were changes in HbA1c and body weight at week 14.<b> </b>The originally randomized interventions were continued to week 54.<b> </b>Liver damage biomarkers and liver fibrosis algorithms were assessed.</p> <p><b>Results</b>: Cotadutide significantly decreased HbA1c and body weight at weeks 14 and 54 versus placebo (all <i>P</i><0.001). Improvements in lipid profile, aspartate aminotransferase and alanine aminotransferase levels, <a>PRO-C3 level, fibrosis-4 index</a>, and <a>nonalcoholic fatty liver disease fibrosis score</a> were observed with cotadutide 300µg versus placebo, but not with liraglutide. Weight loss with cotadutide 200µg was similar to liraglutide 1.8mg, and greater with cotadutide 300µg versus liraglutide 1.8mg. <a>The most common adverse events with cotadutide (nausea, 35%; vomiting, 17%) decreased over time. </a></p> <p><b>Conclusions: </b>Cotadutide treatment for 54 weeks improved glycemic control and weight loss in participants with overweight/obesity and type 2 diabetes. Ad hoc analyses demonstrated improvements in hepatic parameters and support further evaluation of cotadutide in NASH. </p>

scholarly journals Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults with Overweight or Obesity and Type 2 Diabetes Mellitus: A 54-Week Randomized Phase 2b Study

2021 ◽  
Author(s):  
Rajaa Nahra ◽  
Tao Wang ◽  
Kishore M. Gadde ◽  
Jan Oscarsson ◽  
Michael Stumvoll ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Body Weight ◽  
Ad Hoc ◽  
Open Label ◽  
Double Blind ◽  
Glucagon Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Design And Methods

<a><b>Objective: </b></a>Cotadutide, a <a>dual GLP-1 and glucagon receptor agonist</a>, is under development for nonalcoholic steatohepatitis (NASH) and type 2 diabetes. The effects of cotadutide on hepatic and metabolic parameters were evaluated in participants with overweight/obesity and type 2 diabetes. <p><b>Research Design and Methods:</b> In this phase 2b study, 834 adults with BMI ≥25kg/m<sup>2</sup> and type 2 diabetes inadequately controlled with metformin (glycated hemoglobin A1c [HbA1c] of 7.0%─10.5% [53─91 mmol/mol]) were randomized to double-blind cotadutide 100µg (n=100), 200µg (n=256), or 300µg (n=256), placebo (n=110), or open-label liraglutide 1.8mg (n=110), all administered subcutaneously (NCT03235050). Coprimary endpoints were changes in HbA1c and body weight at week 14.<b> </b>The originally randomized interventions were continued to week 54.<b> </b>Liver damage biomarkers and liver fibrosis algorithms were assessed.</p> <p><b>Results</b>: Cotadutide significantly decreased HbA1c and body weight at weeks 14 and 54 versus placebo (all <i>P</i><0.001). Improvements in lipid profile, aspartate aminotransferase and alanine aminotransferase levels, <a>PRO-C3 level, fibrosis-4 index</a>, and <a>nonalcoholic fatty liver disease fibrosis score</a> were observed with cotadutide 300µg versus placebo, but not with liraglutide. Weight loss with cotadutide 200µg was similar to liraglutide 1.8mg, and greater with cotadutide 300µg versus liraglutide 1.8mg. <a>The most common adverse events with cotadutide (nausea, 35%; vomiting, 17%) decreased over time. </a></p> <p><b>Conclusions: </b>Cotadutide treatment for 54 weeks improved glycemic control and weight loss in participants with overweight/obesity and type 2 diabetes. Ad hoc analyses demonstrated improvements in hepatic parameters and support further evaluation of cotadutide in NASH. </p>

scholarly journals Further improvement in glycemic control after switching from exenatide two times per day to exenatide once-weekly autoinjected suspension in patients with type 2 diabetes: 52-week results from the DURATION-NEO-1 study

2020 ◽  
Vol 8 (1) ◽  
pp. e000773
Author(s):  
Carol H Wysham ◽  
Julio Rosenstock ◽  
Marion L Vetter ◽  
Hui Wang ◽  
Elise Hardy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Phase Iii ◽  
Open Label ◽  
Open Label Study ◽  
Registration Number ◽  
Efficacy Measures ◽  
Design And Methods ◽  
To Receive

IntroductionInvestigate the effects of switching from two times per day exenatide to once-weekly exenatide administered by autoinjector (exenatide once-weekly suspension by autoinjector (QWS-AI)) or treatment with exenatide QWS-AI for 1 year.Research design and methodsIn this phase III open-label study, adults with type 2 diabetes were randomized to receive exenatide QWS-AI (2 mg) or exenatide two times per day (5 mcg for 4 weeks, followed by 10 mcg) for 28 weeks. During a subsequent non-randomized 24-week extension, patients who received exenatide two times per day were switched to exenatide QWS-AI and those randomized to exenatide QWS-AI continued this treatment. Efficacy measures included changes from baseline in glycated hemoglobin (A1C), fasting plasma glucose (FPG), and body weight.ResultsIn total, 315 patients (mean baseline A1C of 8.5%) completed the initial 28 weeks of randomized treatment with exenatide QWS-AI (n=197) or exenatide two times per day (n=118) and were included in the 24-week extension (mean A1C of 7.0% and 7.3%, respectively, at week 28). From weeks 28–52, patients who switched from exenatide two times per day to exenatide QWS-AI had additional A1C reductions of approximately 0.5% (mean A1C change from baseline of –1.4% at week 52) and further reductions from baseline in FPG. Patients who continued exenatide QWS-AI treatment for 52 weeks showed clinically relevant A1C reductions (mean A1C change from baseline of –1.3% at week 52). Body-weight reductions achieved through week 28 were sustained at week 52 in both groups. There were no unexpected safety concerns or changes in the safety profile among patients who switched from exenatide two times per day to exenatide QWS-AI or those who continued exenatide QWS-AI treatment for 52 weeks.ConclusionsSwitching from exenatide two times per day to exenatide QWS-AI resulted in further A1C reductions and maintenance of earlier decreases in body weight, while continued therapy with exenatide QWS-AI for 52 weeks maintained A1C and body-weight reductions, without additional safety or tolerability concerns.Trial registration numberNCT01652716.

scholarly journals Outcomes of a Digitally Delivered Low-Carbohydrate Type 2 Diabetes Self-Management Program: 1-Year Results of a Single-Arm Longitudinal Study (Preprint)

2017 ◽  
Author(s):  
Laura R Saslow ◽  
Charlotte Summers ◽  
James E Aikens ◽  
David J Unwin
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Body Weight ◽  
Glycemic Control ◽  
Management Program ◽  
Open Label ◽  
Post Intervention ◽  
Self Monitoring ◽  
Quasi Experimental

BACKGROUND Type 2 diabetes mellitus has serious health consequences, including blindness, amputation, stroke, and dementia, and its annual global costs are more than US $800 billion. Although typically considered a progressive, nonreversible disease, some researchers and clinicians now argue that type 2 diabetes may be effectively treated with a carbohydrate-reduced diet. OBJECTIVE Our objective was to evaluate the 1-year outcomes of the digitally delivered Low-Carb Program, a nutritionally focused, 10-session educational intervention for glycemic control and weight loss for adults with type 2 diabetes. The program reinforces carbohydrate restriction using behavioral techniques including goal setting, peer support, and behavioral self-monitoring. METHODS The study used a quasi-experimental research design comprised of an open-label, single-arm, pre-post intervention using a sample of convenience. From adults with type 2 diabetes who had joined the program and had a complete baseline dataset, we randomly selected participants to be followed for 1 year (N=1000; mean age 56.1, SD 15.7 years; 59.30% (593/1000) women; mean glycated hemoglobin A1c (HbA1c) 7.8%, SD 2.1%; mean body weight 89.6 kg, SD 23.1 kg; taking mean 1.2, SD 1.01 diabetes medications). RESULTS Of the 1000 study participants, 708 (70.80%) individuals reported outcomes at 12 months, 672 (67.20%) completed at least 40% of the lessons, and 528 (52.80%) completed all lessons of the program. Of the 743 participants with a starting HbA1c at or above the type 2 diabetes threshold of 6.5%, 195 (26.2%) reduced their HbA1c to below the threshold while taking no glucose-lowering medications or just metformin. Of the participants who were taking at least one hypoglycemic medication at baseline, 40.4% (289/714) reduced one or more of these medications. Almost half (46.40%, 464/1000) of all participants lost at least 5% of their body weight. Overall, glycemic control and weight loss improved, especially for participants who completed all 10 modules of the program. For example, participants with elevated baseline HbA1c (≥7.5%) who engaged with all 10 weekly modules reduced their HbA1c from 9.2% to 7.1% (P<.001) and lost an average of 6.9% of their body weight (P<.001). CONCLUSIONS Especially for participants who fully engage, an online program that teaches a carbohydrate-reduced diet to adults with type 2 diabetes can be effective for glycemic control, weight loss, and reducing hypoglycemic medications.

How to Maintain a Healthy Body Weight

2006 ◽  
Vol 76 (4) ◽  
pp. 208-215 ◽  
Author(s):  
Astrup
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Body Weight ◽  
Glycemic Index ◽  
Dairy Products ◽  
Weight Control ◽  
Healthy Body Weight ◽  
Healthy Body

The epidemic of both obesity and type 2 diabetes is due to environmental factors, but the individuals developing the conditions possess a strong genetic predisposition. Observational surveys and intervention studies have shown that excess body fatness is the major environmental cause of type 2 diabetes, and that even a minor weight loss can prevent its development in high-risk subjects. Maintenance of a healthy body weight in susceptible individuals requires 45–60 minutes physical activity daily, a fat-reduced diet with plenty of fruit, vegetables, whole grain, and lean meat and dairy products, and moderate consumption of calorie containing beverages. The use of table values to predict the glycemic index of meals is of little – if any – value, and the role of a low-glycemic index diet for body weight control is controversial. The replacement of starchy carbohydrates with protein from lean meat and lean dairy products enhances satiety, and facilitate weight control. It is possible that dairy calcium also promotes weight loss, although the mechanism of action remains unclear. A weight loss of 5–10% can be induced in almost all obese patients providing treatment is offered by a professional team consisting of a physician and dieticians or nurses trained to focus on weight loss and maintenance. Whereas increasing daily physical activity and regular exercise does not significantly effect the rate of weight loss in the induction phase, it plays an important role in the weight maintenance phase due to an impact on daily energy expenditure and also to a direct enhancement of insulin sensitivity.

scholarly journals Long-term efficacy and safety of oral semaglutide and the effect of switching from sitagliptin to oral semaglutide in patients with type 2 diabetes: a 52-week, randomized, open-label extension of the PIONEER 7 trial

2020 ◽  
Vol 8 (2) ◽  
pp. e001649
Author(s):  
John B Buse ◽  
Bruce W Bode ◽  
Ann Mertens ◽  
Young Min Cho ◽  
Erik Christiansen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Dose Adjustment ◽  
Main Phase ◽  
Open Label ◽  
Open Label Extension ◽  
Registration Number ◽  
Flexible Dose

IntroductionThe PIONEER 7 trial demonstrated superior glycemic control and weight loss with once-daily oral semaglutide with flexible dose adjustment versus sitagliptin 100 mg in type 2 diabetes. This 52-week extension evaluated long-term oral semaglutide treatment and switching from sitagliptin to oral semaglutide.Research design and methodsA 52-week, open-label extension commenced after the 52-week main phase. Patients on oral semaglutide in the main phase continued treatment (n=184; durability part); those on sitagliptin were rerandomized to continued sitagliptin (n=98) or oral semaglutide (n=100; initiated at 3 mg) (switch part). Oral semaglutide was dose-adjusted (3, 7, or 14 mg) every 8 weeks based on glycated hemoglobin (HbA1c) (target <7.0% (<53 mmol/mol)) and tolerability. Secondary endpoints (no primary) included changes in HbA1c and body weight.ResultsIn the durability part, mean (SD) changes in HbA1c and body weight from week 0 were –1.5% (0.8) and –1.3% (1.0) and –2.8 kg (3.8) and –3.7 kg (5.2) at weeks 52 and 104, respectively. In the switch part, mean changes in HbA1c from week 52 to week 104 were –0.2% for oral semaglutide and 0.1% for sitagliptin (difference –0.3% (95% CI –0.6 to 0.0); p=0.0791 (superiority not confirmed)). More patients achieved HbA1c <7.0% with oral semaglutide (52.6%) than sitagliptin (28.6%; p=0.0011) and fewer received rescue medication (9% vs 23.5%). Respective mean changes in body weight were –2.4 kg and –0.9 kg (difference –1.5 kg (95% CI –2.8 to –0.1); p=0.0321). Gastrointestinal adverse events were the most commonly reported with oral semaglutide.ConclusionsLong-term oral semaglutide with flexible dose adjustment maintained HbA1c reductions, with additional body weight reductions, and was well tolerated. Switching from sitagliptin to flexibly dosed oral semaglutide maintained HbA1c reductions, helped more patients achieve HbA1c targets with less use of additional glucose-lowering medication, and offers the potential for additional reductions in body weight.Trial registration numberNCT02849080.

scholarly journals Durable Effects of iGlarLixi Up to 52 Weeks in Type 2 Diabetes: The LixiLan-G Extension Study

2021 ◽  
Author(s):  
Lawrence Blonde ◽  
Julio Rosenstock ◽  
Juan Frias ◽  
Andreas L. Birkenfeld ◽  
Elisabeth Niemoeller ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fixed Ratio ◽  
Efficacy And Safety ◽  
Open Label ◽  
Once Daily ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Design And Methods ◽  
Extension Period

<b>Objective</b> <p><a>In the LixiLan-G trial, switching to iGlarLixi, a once-daily titratable fixed-ratio combination of insulin glargine </a>100 units/mL and the glucagon-like peptide-1 receptor agonist (GLP-1 RA) lixisenatide, improved glucose control in type 2 diabetes (T2D) uncontrolled with GLP-1 RAs over 26 weeks versus continuing prior GLP-1 RA. A prespecified, 26-week, single-arm extension of LixiLan-G aimed to determine the durability of iGlarLixi efficacy and safety over 52 weeks. </p> <p><b>Research Design and Methods</b></p> <p>Participants with T2D uncontrolled by GLP-1 RAs (HbA<sub>1c</sub> 7–9 % [53–75 mmol/mol]) were initially randomized to switch to iGlarLixi or continue prior GLP-1 RA. Those randomized to iGlarLixi who completed the 26-week primary endpoint period could continue iGlarLixi open-label treatment over a 26-week extension to assess durability of efficacy and safety.</p> <p><b>Results</b></p> <p>Glycemic control achieved with iGlarLixi at week 26 (mean HbA<sub>1c</sub> 6.7 % [50 mmol/mol]) was maintained at week 52 (mean HbA<sub>1c</sub> 6.7 % [50 mmol/mol]; mean ± standard deviation change from baseline at week 52: −1.0 ± 0.9 % [11 ± 10 mmol/mol]). Proportions of participants reaching HbA<sub>1c</sub> <7 % (53 mmol/mol) with iGlarLixi were similar at week 26 (62%) and 52 (64%), as were those reaching this target without documented symptomatic (<3.0 mmol/L) hypoglycemia (57% and 58%). Safety of iGlarLixi was similar at weeks 26 and 52, with low rates of documented symptomatic hypoglycemia and gastrointestinal events.</p> <p><b>Conclusions</b></p> The efficacy and safety of iGlarLixi at the end of the 26-week randomized treatment period was maintained over the 26-week extension period in the LixiLan-G trial.

Abstract 11616: Effect of a Lifestyle Weight Loss Intervention on Visceral Fat and Glycemic Control Among Individuals With and Without Type 2 Diabetes

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Soohyun Nam ◽  
Soohyun Nam ◽  
Devon A Dobrosielski ◽  
Kerry J Stewart
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Body Weight ◽  
Glycemic Control ◽  
Aerobic Fitness ◽  
Visceral Fat ◽  
Subcutaneous Fat ◽  
Moderate Intensity ◽  
Weight Loss Diet

Background: Though a high amount of visceral fat is associated with insulin resistance, which can lead to type 2 diabetes (T2D) and cardiovascular diseases (CVDs), less is known about whether lifestyle modification (weight loss diet and exercise) induced changes in visceral fat are associated with improvements in glycemia. Methods: We randomized 77 individuals aged 35-65 years with T2D or pre-diabetes to 6-months of weight loss diet (D); or D combined with supervised moderate-intensity exercise training (D+E). Study measures were total abdominal, visceral and subcutaneous fat volumes by magnetic resonance imaging, aerobic fitness expressed as VO 2 peak during treadmill testing, body mass index (BMI), and HbA1c levels from blood samples. Results: Of 77 subjects (mean age, 54.8±7.8 years; mean BMI, 34.5 ± 4.7 kg/m 2 , women, 77.9%; Whites-65%, Blacks-34%, Asians-1%), n=37 had T2D and n=40 had pre-diabetes. At 6 months, both D and D+E groups improved from baseline (p<0.05 for all) but did not differ in their changes for body weight (D: -6.04 ± 4.54 kg; D+E: -6.68 ± 4.48 kg, p= 0.61 for the group differences in change), abdominal total fat (D: -101.93 ± 68.67 cm 2 ; D+E:-104.16 ± 72.37 cm 2 , p= 0.92), visceral fat (D:-25.53 ± 39.44 cm 2 ; D+E:,-23.24 ± 35.62 cm 2 , p=0.85), HbA1c (D:0.04 ± 0.46%; D+E:0.03 ± 0.63%, p=0.96), and VO 2 peak (D: 2.26 ± 3.92 ml/kg/min ; D+E:3.71 ± 2.65 ml/kg/min, p=0.11). In a multivariate analysis, adjusting for baseline visceral fat, T2D status, body weight loss and increases in aerobic fitness, a reduction in HbA1c (β=-0.49, p =0.007) was associated with a reduction in visceral fat (R 2 =0.34, p=0.02). Conclusion: The key finding was that diet or diet plus exercise-mediated reductions in visceral fat was associated with reduced HbA1c among individuals with T2D or pre-diabetes. These data contribute to growing body of evidence of the benefits of reducing abdominal obesity, in this case, resulting in better glycemic control in T2D and pre-diabetes.

scholarly journals Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Kausik K. Ray ◽  
Stefano Del Prato ◽  
Dirk Müller-Wieland ◽  
Bertrand Cariou ◽  
Helen M. Colhoun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Open Label ◽  
Double Blind ◽  
Mixed Dyslipidemia

Abstract Background Individuals with diabetes often have high levels of atherogenic lipoproteins and cholesterol reflected by elevated low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and LDL particle number (LDL-PN). The presence of atherosclerotic cardiovascular disease (ASCVD) increases the risk of future cardiovascular events. We evaluated the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, alirocumab, among individuals with type 2 diabetes (T2DM), high LDL-C or non-HDL-C, and established ASCVD receiving maximally tolerated statin in ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) and DM-INSULIN (NCT02585778). Methods In DM-DYSLIPIDEMIA, individuals with T2DM and mixed dyslipidemia (non-HDL-C ≥ 100 mg/dL; n = 413) were randomized to open-label alirocumab 75 mg every 2 weeks (Q2W) or usual care (UC) for 24 weeks, with UC options selected before stratified randomization. In DM-INSULIN, insulin-treated individuals with T2DM (LDL-C ≥ 70 mg/dL; n = 441) were randomized in a double-blind fashion to alirocumab 75 mg Q2W or placebo for 24 weeks. Study participants also had a glycated hemoglobin < 9% (DM-DYSLIPIDEMIA) or < 10% (DM-INSULIN). Alirocumab dose was increased to 150 mg Q2W at week 12 if week 8 LDL-C was ≥ 70 mg/dL (DM-INSULIN) or non-HDL-C was ≥ 100 mg/dL (DM-DYSLIPIDEMIA). Lipid reductions and safety were assessed in patients with ASCVD from these studies. Results This analysis included 142 DM-DYSLIPIDEMIA and 177 DM-INSULIN participants with ASCVD, including 95.1% and 86.4% with coronary heart disease, and 32.4% and 49.7% with microvascular diabetes complications, respectively. At week 24, alirocumab significantly reduced LDL-C, non-HDL-C, ApoB, and LDL-PN from baseline versus control. This translated into a greater proportion of individuals achieving non-HDL-C < 100 mg/dL (64.6% alirocumab/23.8% UC [DM-DYSLIPIDEMIA]; 65.4% alirocumab/14.9% placebo [DM-INSULIN]) and ApoB < 80 mg/dL (75.1% alirocumab/35.4% UC and 76.8% alirocumab/24.8% placebo, respectively) versus control at week 24 (all P < 0.0001). In pooling these studies, 66.4% (alirocumab) and 67.0% (control) of individuals reported treatment-emergent adverse events. The adverse event pattern was similar with alirocumab versus controls. Conclusions Among individuals with T2DM and ASCVD who had high non-HDL-C/LDL-C levels despite maximally tolerated statin, alirocumab significantly reduced atherogenic cholesterol and LDL-PN versus control. Alirocumab was generally well tolerated. Trial registration Clinicaltrials.gov. NCT02642159. Registered 30 December 2015 and Clinicaltrials.gov. NCT02585778. Registered 23 October 2015

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