Lifestyle changes observed among adults participating in a family- and community-based intervention for diabetes prevention in Europe : the 1st year results of the Feel4Diabetes-study

The Feel4Diabetes intervention was a school and community-based intervention aiming to promote healthy lifestyle and tackle obesity and obesity-related metabolic risk factors for the prevention of type 2 diabetes (T2D) among families at risk of developing this disease. The current study aims to present the results on lifestyle behaviors obtained from parents during the first year of the Feel4Diabetes intervention. This multicomponent intervention had a cluster randomized design and was implemented in Belgium, Bulgaria, Finland, Greece, Hungary and Spain over two years (2016–2018). Standardized protocols and procedures were used by the participating centers in all countries to collect data on parents’ lifestyle behaviors (diet, physical activity, sedentary behavior). The Feel4Diabetes intervention was registered at clinicaltrials.gov (registration number: NCT02393872). In total, 2110 high-risk parents participated in the baseline and 12-month follow-up examination measurements. Participants allocated to the intervention group reduced their daily consumption of sugary drinks (p = 0.037) and sweets (p = 0.031) and their daily screen time (p = 0.032), compared with the control group. In addition, participants in the intervention group in Greece and Spain increased their consumption of breakfast (p = 0.034) and fruits (p = 0.029), while in Belgium and Finland they increased their water intake (p = 0.024). These findings indicate that the first year of the Feel4Diabetes intervention resulted in the improvement of certain lifestyle behaviors in parents from high-risk families

Efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial

Background: Semaglutide is an effective treatment for type 2 diabetes; however, 20–30% of patients given semaglutide 1·0 mg do not reach glycaemic treatment goals. We aimed to investigate the efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in adults with inadequately controlled type 2 diabetes on a stable dose of metformin with or without a sulfonylurea. Methods: We did a 40-week, randomised, active-controlled, parallel-group, double-blind, phase 3B trial (SUSTAIN FORTE) at 125 outpatient clinics in ten countries. Participants (≥18 years) with inadequately controlled type 2 diabetes (HbA1c 8·0–10·0%) with metformin and with or without sulfonylurea were randomly assigned (1:1) by an interactive web-response system to 2·0 mg or 1·0 mg once-weekly semaglutide. Participants, site personnel, the clinical study group, and investigators were masked to the randomised treatment. Outcomes included change from baseline at week 40 in HbA1c (primary outcome) and bodyweight (secondary confirmatory outcome), evaluated through trial product estimand (no treatment discontinuation or without rescue medication) and treatment policy estimand (regardless of treatment discontinuation or rescue medication) strategies. This study is registered with ClinicalTrials.gov, NCT03989232; EudraCT, 2018-004529-96; and WHO, U1111-1224-5162. Findings: Between June 19 and Nov 28, 2019, of 1515 adults assessed for eligibility, 961 participants (mean age 58·0 years [SD 10·0]; 398 [41%] women) were included. Participants were randomly assigned to once-weekly semaglutide 2·0 mg (n=480 [50%]) or 1·0 mg (n=481 [50%]); 462 (96%) patients in the semaglutide 2·0 mg group and 471 (98%) in the semaglutide 1·0 mg group completed the trial. Mean baseline HbA1c was 8·9% (SD 0·6; 73·3 mmol/mol [SD 6·9]) and BMI was 34·6 kg/m2 (SD 7·0). Mean change in HbA1c from baseline at week 40 was −2·2 percentage points with semaglutide 2·0 mg and −1·9 percentage points with semaglutide 1·0 mg (estimated treatment difference [ETD] −0·23 percentage points [95% CI −0·36 to −0·11]; p=0·0003; trial product estimand) and −2·1 percentage points with semaglutide 2·0 mg and −1·9 percentage points with semaglutide 1·0 mg (ETD −0·18 percentage points [–0·31 to −0·04]; p=0·0098; treatment policy estimand). Mean change in bodyweight from baseline at week 40 was −6·9 kg with semaglutide 2·0 mg and −6·0 kg with semaglutide 1·0 mg (ETD −0·93 kg [95% CI −1·68 to −0·18]; p=0·015; trial product estimand) and −6·4 kg with semaglutide 2·0 mg and −5·6 kg with semaglutide 1·0 mg (ETD −0·77 kg [–1·55 to 0·01]; p=0·054; treatment policy estimand). Gastrointestinal disorders were the most commonly reported adverse events (163 [34%] in the 2·0 mg group and 148 [31%] in the 1·0 mg group). Serious adverse events were similar between treatment groups, reported for 21 (4%) participants given semaglutide 2·0 mg and 25 (5%) participants given semaglutide 1·0 mg. Three deaths were reported during the trial (one in the semaglutide 1·0 mg group and two in the semaglutide 2·0 mg group). Interpretation: Semaglutide 2·0 mg was superior to 1·0 mg in reducing HbA1c, with additional bodyweight loss and a similar safety profile. This higher dose provides a treatment intensification option for patients with type 2 diabetes treated with semaglutide in need of additional glycaemic control. Funding: Novo Nordisk

Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes: The LEAD (Liraglutide Effect and Action in Diabetes)-2 study

OBJECTIVE—The efficacy and safety of adding liraglutide (a glucagon-like peptide-1 receptor agonist) to metformin were compared with addition of placebo or glimepiride to metformin in subjects previously treated with oral antidiabetes (OAD) therapy

Feel4Diabetes healthy diet score: Development and evaluation of clinical validity

Background: The aim of this paper is to present the development of the Feel4Diabetes Healthy Diet Score and to evaluate its clinical validity. Methods: Study population consisted of 3268 adults (63% women) from high diabetes risk families living in 6 European countries. Participants filled in questionnaires at baseline and after 1 year, reflecting the dietary goals of the Feel4Diabetes intervention. Based on these questions the Healthy Diet Score was constructed, consisting of the following components: breakfast, vegetables, fruit and berries, sugary drinks, whole-grain cereals, nuts and seeds, low-fat dairy products, oils and fats, red meat, sweet snacks, salty snacks, and family meals. Maximum score for each component was set based on its estimated relative importance regarding T2DM risk, higher score indicating better quality of diet. Clinical measurements included height, weight, waist circumference, heart rate, blood pressure, and fasting blood sampling, with analyses of glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides. Analysis of (co) variance was used to compare the Healthy Diet Score and its components between countries and sexes using baseline data, and to test differences in clinical characteristics between score categories, adjusted for age, sex and country. Pearson''s correlations were used to study the association between changes from baseline to year 1 in the Healthy Diet Score and clinical markers. To estimate reproducibility, Pearson''s correlations were studied between baseline and 1 year score, within the control group only. Results: The mean total score was 52.8 ± 12.8 among women and 46.6 ± 12.8 among men (p < 0.001). The total score and its components differed between countries. The change in the Healthy Diet Score was significantly correlated with changes in BMI, waist circumference, and total and LDL cholesterol. The Healthy Diet Score as well as its components at baseline were significantly correlated with the values at year 1, in the control group participants. Conclusion: The Feel4Diabetes Healthy Diet Score is a reproducible method to capture the dietary information collected with the Feel4Diabetes questionnaire and measure the level of and changes in the adherence to the dietary goals of the intervention. It gives a simple parameter that associates with clinical risk factors in a meaningful manner

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the LEAD-2 study

Aims: To investigate efficacy and safety of dual therapy with liraglutide and metformin in comparison to glimepiride and metformin, and metformin monotherapy over 2years in patients with type 2 diabetes. Methods: In the 26-week the Liraglutide Effect and Action in Diabetes (LEAD)-2 core trial, patients (n=1091) were randomized (2:2:2:1:2) to liraglutide (0.6, 1.2 or 1.8mg once-daily), placebo or glimepiride; all with metformin. Patients were enrolled if they were 18-80years old with HbA1c 7.0-11.0% (previous monotherapy ≥3months), or 7.0-10.0% (previous combination therapy ≥3months), and body mass index ≤40kg/m2. Patients completing the 26-week double-blinded phase could enter an 18-month open-label extension. Results: HbA1c decreased significantly with liraglutide (0.4% with 0.6mg, 0.6% with 1.2 and 1.8mg) versus 0.3% increase with metformin monotherapy (p&lt;0.0001). HbA1c decrease with liraglutide was non-inferior versus 0.5% decrease with glimepiride. Liraglutide groups experienced significant weight loss (2.1, 3.0 and 2.9kg with 0.6, 1.2 and 1.8mg, respectively) compared to weight gain (0.7kg) with glimepiride (p&lt;0.0001). Weight loss with liraglutide 1.2 and 1.8mg was significantly greater than with metformin monotherapy (1.8kg; p=0.0185 and p=0.0378 for 1.2 and 1.8mg, respectively). The occurrence of minor hypoglycaemia was &lt;5.0% in all liraglutide groups, significantly less than with glimepiride (24.0%; p&lt;0.0001). Liraglutide was well tolerated overall: gastrointestinal events were more common than with glimepiride or metformin monotherapy, but occurrence decreased with time. Conclusions: Liraglutide provided sustained glycaemic control over 2 years comparable to that provided by glimepiride. Liraglutide was well tolerated, and was associated with weight loss and a low rate of hypoglycaemia. © 2012 Blackwell Publishing Ltd

Efficacy and safety of once-weekly semaglutide 2.0 mg versus 1.0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial

Background Semaglutide is an effective treatment for type 2 diabetes; however, 20-30% of patients given semaglutide 1.0 mg do not reach glycaemic treatment goals. We aimed to investigate the efficacy and safety of once-weekly semaglutide 2.0 mg versus 1.0 mg in adults with inadequately controlled type 2 diabetes on a stable dose of metformin with or without a sulfonylurea. Methods We did a 40-week, randomised, active-controlled, parallel-group, double-blind, phase 3B trial (SUSTAIN FORTE) at 125 outpatient clinics in ten countries. Participants (&gt;= 18 years) with inadequately controlled type 2 diabetes (HbA1c 8.0-10.0%) with metformin and with or without sulfonylurea were randomly assigned (1:1) by an interactive web-response system to 2.0 mg or 1.0 mg once-weekly semaglutide. Participants, site personnel, the clinical study group, and investigators were masked to the randomised treatment. Outcomes included change from baseline at week 40 in HbA1c (primary outcome) and bodyweight (secondary confirmatory outcome), evaluated through trial product estimand (no treatment discontinuation or without rescue medication) and treatment policy estimand (regardless of treatment discontinuation or rescue medication) strategies. This study is registered with ClinicalTrials.gov, NCT03989232; EudraCT, 2018-004529-96; and WHO, U1111-1224-5162. Findings Between June 19 and Nov 28, 2019, of 1515 adults assessed for eligibility, 961 participants (mean age 58.0 years [SD 10.0]; 398 [41%] women) were included. Participants were randomly assigned to once-weekly semaglutide 2.0 mg (n=480 [50%]) or 1.0 mg (n=481 [50%]); 462 (96%) patients in the semaglutide 2.0 mg group and 471 (98%) in the semaglutide 1.0 mg group completed the trial. Mean baseline HbA1c was 8.9% (SD 0.6; 73.3 mmol/mol [SD 6.9]) and BMI was 34.6 kg/m2 (SD 7.0). Mean change in HbA1c from baseline at week 40 was -2.2 percentage points with semaglutide 2.0 mg and -1.9 percentage points with semaglutide 1.0 mg (estimated treatment difference [ETD] -0.23 percentage points [95% CI -0.36 to -0.11]; p=0.0003; trial product estimand) and -2.1 percentage points with semaglutide 2.0 mg and -1.9 percentage points with semaglutide 1.0 mg (ETD -0.18 percentage points [-0.31 to -0.04]; p=0.0098; treatment policy estimand). Mean change in bodyweight from baseline at week 40 was -6.9 kg with semaglutide 2.0 mg and -6.0 kg with semaglutide 1.0 mg (ETD -0.93 kg [95% CI -1.68 to -0.18]; p=0.015; trial product estimand) and -6.4 kg with semaglutide 2.0 mg and -5.6 kg with semaglutide 1.0 mg (ETD -0.77 kg [-1.55 to 0.01]; p=0.054; treatment policy estimand). Gastrointestinal disorders were the most commonly reported adverse events (163 [34%] in the 2.0 mg group and 148 [31%] in the 1.0 mg group). Serious adverse events were similar between treatment groups, reported for 21 (4%) participants given semaglutide 2.0 mg and 25 (5%) participants given semaglutide 1.0 mg. Three deaths were reported during the trial (one in the semaglutide 1.0 mg group and two in the semaglutide 2.0 mg group). Interpretation Semaglutide 2.0 mg was superior to 1.0 mg in reducing HbA1c, with additional bodyweight loss and a similar safety profile. This higher dose provides a treatment intensification option for patients with type 2 diabetes treated with semaglutide in need of additional glycaemic control. Copyright (C) 2021 Elsevier Ltd. All rights reserved