scholarly journals Clinical Effectiveness and Safety of Once-Weekly GLP-1 Receptor Agonist Dulaglutide as Add-On to Metformin or Metformin Plus Insulin Secretagogues in Obesity and Type 2 Diabetes

2021 ◽  
Vol 10 (5) ◽  
pp. 985
Author(s):  
Maria Mirabelli ◽  
Eusebio Chiefari ◽  
Vera Tocci ◽  
Patrizia Caroleo ◽  
Stefania Giuliano ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Body Weight ◽  
Receptor Agonist ◽  
Drug Discontinuation ◽  
Baseline Body Mass Index ◽  
Study Cohort ◽  
Insulin Secretagogues

Aims and methods: The aim of this monocentric retrospective observational study was to evaluate the 18-month safety and effectiveness of GLP-1 receptor agonist (GLP-1 RA) dulaglutide (DU) 1.5 mg/once weekly as an add-on to metformin (MET) or MET plus conventional insulin secretagogues in a study cohort with excess body weight and type 2 diabetes (T2D). Comparative efficacy versus liraglutide (LIRA) 1.2–1.8 mg/once daily in a study sample naïve to GLP-1 RAs, frequency matching for age, gender, T2D duration, degree of glycemic impairment, cardiovascular comorbidities, and medications, was addressed as a secondary aim. Clinical and biochemical data for efficacy outcomes and information on drug discontinuation due to adverse events (AEs) were collected from digital records. Results: Initial analysis included 126 overweight and obese T2D patients (48.4% females). Out of these, 13 discontinued DU due to moderate–severe gastrointestinal AEs after a mean follow-up of 6 (4 standard deviations (SD)) months, while 65 completed 18 months of continuous therapy. At 6 months, there was a significant mean HbA1c reduction of −0.85% (1.17 SD) with respect to baseline values (p < 0.001), which remained stable during 18 months follow-up. These results were accompanied by a moderate weight loss sustained over time, with a mean reduction of −2.0% (4.3 SD) at 6 months and −1.3% (4.8 SD) at 18 months (p = 0.091). At univariate analysis, a negative correlation between baseline body mass index (BMI) and risk of drug discontinuation due to gastrointestinal AEs was observed. The protective effect of obesity against drug discontinuation was confirmed by logistic regression analysis. Neither gender, nor age, nor T2D duration, nor concomitant conventional insulin secretagogue use, nor switching to DU from other GLP-1 RAs influenced its long-term effectiveness. However, higher baseline HbA1c values emerged as predictors of clinically relevant efficacy outcomes, either in terms of HbA1c reduction ≥ 0.5% or body weight loss ≥ 5%. The efficacy outcomes were corroborated by head-to-head comparison with LIRA, a GLP-1 RA with durable beneficial effects on glycemic control and body weight in real-world experiences. With the advantage of once-weekly administration, at 18-month follow-up, a significantly larger fraction of patients on DU therapy reached glycemic targets (HbA1c ≤ 7.0%) when compared to those on LIRA: from 14.8% at baseline (both groups) to 64.8% with DU and 42.6% with LIRA (p = 0.033). Conclusions: Although limited by a retrospective design and lack of constant up-titration for LIRA to the highest dose, these findings indicate that the beneficial responses to DU on a background of MET or MET plus insulin secretagogues are durable, especially in the presence of obesity and greater HbA1c impairment.

scholarly journals Long-Term Effectiveness and Safety of Once Weekly Dulaglutide as Add-on to Metformin or Metformin Plus Insulin Secretagogues in Obesity and Type 2 Diabetes

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A333-A334
Author(s):  
Maria Mirabelli ◽  
Eusebio Chiefari ◽  
Vera Tocci ◽  
Luigi Puccio ◽  
Daniela Foti ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Drug Discontinuation ◽  
Excess Body Weight ◽  
Study Cohort ◽  
Beneficial Effects ◽  
Cardiovascular Comorbidities ◽  
Insulin Secretagogues

Abstract Aim of this monocentric retrospective observational study was to evaluate the 18-month effectiveness and safety of once weekly 1.5 mg GLP-1 receptor agonist (GLP-1 RA) dulaglutide (DU) as add-on to metformin (MET) or MET plus conventional insulin secretagogues (SFU/glinide) in a study cohort with excess body weight (BW) and type 2 diabetes (T2D). Comparative efficacy versus once daily 1.2/1.8 mg liraglutide (LIRA) in a study sample naïve to GLP-1 RAs, matching for age, gender, BMI, T2D duration, cardiovascular comorbidities and medications, was addressed as a secondary aim. Clinical and biochemical data for efficacy outcomes and information on drug discontinuation due to adverse events (AEs) were collected from digital records. Initial analysis included 126 overweight and obese T2D patients (48.4% females). Out of these, 13 discontinued DU due to moderate-severe gastrointestinal AEs after a median follow-up of 6 (3 to 8) months, while 65 completed 18 months of continuous therapy. At 6 months, there was a significant median HbA1c reduction of -0.9 (-1.50 to -0.20) % with respect to baseline values (p&lt;0.001), which remained stable during 18 months of follow-up. These results were accompanied by a moderate BW loss sustained over time, with a median reduction of -1.16 (-4,29 to 0.45) % at 6 months and -1.47 (-4.2 to 0.72) % at 18 months (p=0.048). At univariate Spearman analysis, a negative correlation between baseline BMI and risk of drug discontinuation due to gastrointestinal AEs was observed. The protective effect of obesity (BMI ≥ 30kg/m2) against drug discontinuation was confirmed by an exploratory logistic regression analysis, while adjusting for confounders [OR 0.211 (95%CI 0.058–0.771), p=0.019]. Neither gender, nor age, nor T2D duration, nor concomitant SUF/glinide use, nor shifting to DU from other GLP-1 RAs influenced its long-term effectiveness. However, higher baseline HbA1c values emerged as predictors of clinically relevant efficacy outcomes, either in form of HbA1c reduction ≥ 0.5% [OR 2.961 (95%CI 1.394–6.290), p=0.005] or BW loss ≥ 5% [OR 2.571 (95%CI 1.171–5.644), p=0.019]. The efficacy outcomes were corroborated by head-to-head comparison with LIRA, a GLP-1 RA with durable beneficial effects on glycemic control and BW in real word scenarios (1). With the advantage of once weekly administration, at 18-month follow-up, a significant larger fraction of patients on DU therapy reached glycemic targets (HbA1c ≤ 7.0%) when compared to those on LIRA: from 14.8% at baseline (both groups) to 64.8% with DU and 42.6% with LIRA (p=0.033). Although limited by a retrospective design and lack of constant up-titration for LIRA to the highest dose, these findings indicate that the beneficial glycometabolic responses to DU on a background of MET or MET plus SFU/glinide are durable, especially in presence of obesity and greater HbA1c impairment. (1) Ref: Mirabelli et al. IJERPH. 2019;17(1):207.

scholarly journals Frequency of self-monitoring of blood glucose in relation to weight loss and A1C during intensive multidisciplinary weight management in patients with type 2 diabetes and obesity

2019 ◽  
Vol 7 (1) ◽  
pp. e000659 ◽  
Author(s):  
Shaheen Tomah ◽  
Noor Mahmoud ◽  
Adham Mottalib ◽  
David M Pober ◽  
Mhd Wael Tasabehji ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Body Weight ◽  
Blood Glucose ◽  
Weight Management ◽  
Average Frequency ◽  
Baseline Body Mass Index ◽  
Self Monitoring ◽  
Median Change

ObjectiveWe evaluated the relationship between frequency of self-monitoring of blood glucose (SMBG) and body weight, A1C, and cardiovascular risk factors in patients with type 2 diabetes (T2D) and obesity enrolled in a 12-week intensive multidisciplinary weight management (IMWM) program.Research design and methodsWe conducted a retrospective analysis of 42 patients who electronically uploaded their SMBG data over 12 weeks of an IMWM program and divided them into tertiles based on their average frequency of SMBG per day. Mean (range) SMBG frequencies were 2.3 (1.1–2.9) times/day, 3.4 (3–3.9) times/day, and 5 (4–7.7) times/day in the lowest, middle, and highest tertiles, respectively. Anthropometric and metabolic parameters were measured at baseline and after 12 weeks of intervention.ResultsParticipants in the highest tertile achieved a median change (IQR) in body weight of −10.4 kg (−7.6 to −14.4 kg) compared with −8.3 kg (−5.2 to −12.2 kg), and −6.9 kg (−4.2 to −8.9 kg) in the middle and lowest tertiles, respectively (p=0.018 for trend). Participants in the highest tertile had a median change (IQR) in A1C of −1.25% (−0.6 to −3.1%) compared with −0.8% (−0.3% to −2%) and −0.5% (−0.2% to −1.2%) in the middle and lowest tertiles, respectively (p=0.048 for trend). The association between change in body weight and SMBG frequency remained significant after adjusting for age, sex, baseline body mass index, diabetes duration, and use of insulin therapy.ConclusionsIncreased frequency of SMBG during IMWM is associated with significantly better weight loss and improvement of A1C in patients with T2D and obesity. These findings may suggest future clinical recommendations aimed at increasing SMBG frequency to achieve the most favorable outcomes.

Association Between Glycosylated Hemoglobin and Intentional Weight Loss in Overweight and Obese Patients With Type 2 Diabetes Mellitus

2012 ◽  
Vol 38 (3) ◽  
pp. 417-426 ◽  
Author(s):  
Ghanshyam Palamaner Subash Shantha ◽  
Anita Ashok Kumar ◽  
Scott Kahan ◽  
Lawrence J. Cheskin
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Type 2 Diabetes Mellitus ◽  
Glycosylated Hemoglobin ◽  
Baseline Body Mass Index ◽  
Study Cohort ◽  
Obese Patients ◽  
Intentional Weight Loss

Purpose The purpose of this study is to assess the relationship between magnitude of weight loss and improvement in percentage A1C (A1C%) among overweight and obese patients with type 2 diabetes mellitus (DM) undergoing weight reduction. Methods Case records of patients enrolled in 2 university-based weight management programs were reviewed. Patients were sampled if they had a diagnosis of DM and had at least 1 documented A1C% reduction from their baseline value. Weight loss treatment was individualized and consisted of a calorie-restricted diet, a behavior modification plan, and a plan for increasing physical activity. Patient weights were measured at bimonthly visits. A1C% was measured every 3 months. Results Seventy-two patients formed the study cohort. Mean baseline body mass index was 35.1 kg/m2, mean age was 52.6 years, and 59% were males. Mean starting A1C% was 8.6. Patients achieved significant mean weight loss (10.7 kg) at study exit. Weight loss of 6.5 kg (4.5% of baseline body weight), 12.2 kg (8.7%), and 15.9 kg (10.3%) was required to reduce A1C% by 0.5, 1, and 1.5, respectively, and it took a mean of 5.6, 8.7, and 10.1 months, respectively, to achieve this. After adjustment for antidiabetic medication intake, for every 10% weight loss, the predicted reduction in A1C% was 0.81. Conclusions Intentional weight loss of 10% can potentially decrease A1C% by 0.81 among patients with type 2 DM. This finding may be clinically useful in encouraging and counseling a patient attempting weight loss.

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.

564-P: Long-Term Follow-up of Glycemic Excursion Minimization (GEM) Compared with Weight Loss in Management of Type 2 Diabetes (T2D)

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 564-P
Author(s):  
DANIEL COX ◽  
MATTHEW A. MONCRIEF ◽  
ANTHONY L. MCCALL
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Long Term Follow Up

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 Lixisenatide is effective and safe as add-on treatment to basal insulin in Asian individuals with type 2 diabetes and different body mass indices: a pooled analysis of data from the GetGoal Studies

2021 ◽  
Vol 9 (1) ◽  
pp. e002290
Author(s):  
Wenhuan Feng ◽  
Weimin Wang ◽  
Ran Meng ◽  
Guangyu Wu ◽  
Minlu Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Body Mass ◽  
Basal Insulin ◽  
Insulin Dose ◽  
Study Endpoint ◽  
Baseline Body Mass Index ◽  
Efficacy And Safety ◽  
Multivariable Regression

IntroductionThis analysis aims to investigate the efficacy and safety of once-daily lixisenatide add-on treatment to basal insulin in Asian individuals with type 2 diabetes, by baseline body mass index (BMI).Research design and methodsData from all Asian participants in the placebo-controlled GetGoal-Duo 1, GetGoal-L, and GetGoal-L-C Studies were pooled and categorized according to the following BMI subgroups:<25 kg/m2, 25–<30 kg/m2 and ≥30 kg/m2. Efficacy and safety of lixisenatide versus placebo were evaluated among BMI subgroups. Multivariable regression analyses were also conducted to explore the potential influence of BMI on efficacy outcomes after adjusting for baseline characteristics.Results555 participants were included (mean age 53.9 years, 52.4% men). No significant differences in treatment effect between the BMI subgroups were observed for the changes from baseline to 24 weeks in glycated hemoglobin (HbA1c), fasting plasma glucose, postprandial glucose (PPG), PPG excursion, body weight, BMI, and basal insulin dose with lixisenatide, as well as the change in basal insulin dose at study endpoint and the proportion of participants achieving an HbA1c <7% at 24 weeks (all p values for interaction >0.15). In the multivariable regression analysis, participants in the lowest BMI group had a smaller reduction in body weight over the 24-week treatment period relative to the highest BMI group (p=0.023).ConclusionsThis post hoc analysis indicates that lixisenatide improved glycemic control regardless of baseline BMI and was well tolerated in Asian individuals unable to achieve their HbA1c target on basal insulin±oral antidiabetic drugs.

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.

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