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Objective: Evidence suggests the increased prevalence of diabetes among South Asian (SA) adolescents is due to their genetic risk profile. The South Asian Adolescent Diabetes Awareness Program (SAADAP) is a pilot intervention for SA youth in Canada with a family history of type 2 diabetes mellitus (T2DM). We sought to investigate changes in (1) diabetes knowledge and associated risk factors, (2) risk perception and (3) health behaviours among adolescents participating in SAADAP. Design: One-group pre-test, post-test design informed by a commitment to community-based participatory research (CBPR). Setting: Sixty-eight adolescents aged 13-17 years with a family history of T2DM participated in SAADAP in a clinical-community setting in Canada. Method: Pre-post questionnaires were administered to evaluate diabetes knowledge and associated risk factors, risk perceptions and health behaviours. Analyses were restricted to 49 participants who attended at least four diabetes education sessions. Results: The mean age of adolescents was 14.5 years, and 57.1% self-identified as girls. The difference in knowledge about the definition, symptoms and complications of T2DM from baseline to post-intervention was 3.32 out of 21 (p < 0.001) among SA youth. There was significant increase in learning about diabetes risk factors (p < 0.001) from baseline to post-intervention. Almost 60% of participants exhibited no change in their risk perception after intervention. Approximately two-thirds of the participants self-reported positive changes in health behaviours after completing the programme. Conclusion: SAADAP showed promising outcomes in raising knowledge and improving health behaviours in SA adolescents with a family history of diabetes. Larger controlled trials with longer follow-up are recommended to support and expand on the current findings.

Aim: To perform a participant‐level post hoc meta‐analysis of Phase 3a trials in type 2 diabetes (T2D) to characterize the hypoglycaemia safety and glycaemic efficacy of once‐weekly insulin icodec (icodec). Materials and Methods: All ONWARDS 1–5 randomized participants were pooled as overall T2D, insulin‐naive, an insulin‐experienced subgroups, and by once‐daily trial comparator (degludec or glargine U100). The main outcomes included incidence and rates of clinically significant and severe hypoglycaemia. Additional endpoints included change in glycated haemoglobin (HbA1c) from baseline and HbA1c target achievement without clinically significant or severe hypoglycaemia. Results: The meta‐analysis comprised 3765 participants (1882 icodec vs. 1883 comparators). In the overall T2D pool, clinically significant hypoglycaemia incidence was similar in the icodec group versus the comparator group (17.9% vs. 16.2%, odds ratio [OR] 1.14, 95% confidence interval [CI] 0.94, 1.38); however, rates were low but significantly higher in the icodec group (1.15 vs. 1.00 episodes/participant‐year of exposure, estimated rate ratio 1.51 [95% CI 1.24, 1.85]). Fewer severe hypoglycaemic episodes occurred with icodec than with comparators (8 vs. 18). A greater reduction in HbA1c occurred with icodec versus comparators, irrespective of subgroup (estimated treatment difference range [−0.10 to −0.29%]; all p < 0.05). Across subgroups, except for the insulin‐experienced subgroup, the odds of achieving HbA1c <53 mmol/mol (7.0%) without clinically significant or severe hypoglycaemia were greater with icodec than with comparators (OR range 1.30–1.55; all p < 0.05). Conclusions: Icodec was associated with a similar incidence but higher rates of clinically significant hypoglycaemia (equating to one additional hypoglycaemic episode every 6 years) and fewer severe hypoglycaemic episodes versus comparators. Our findings also confirmed the greater efficacy of icodec that was demonstrated in the ONWARDS trial programme. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This post hoc analysis assessed continuous glucose monitoring (CGM)–based metrics and hypoglycemia duration with once-weekly insulin icodec versus once-daily basal insulin analogs in insulin-experienced individuals with long-standing type 2 diabetes from two 26-week phase 3a trials (ONWARDS 2 and ONWARDS 4). RESEARCH DESIGN AND METHODS: Time in range (TIR) (3.9–10.0 mmol/L), time above range (TAR) (>10.0 mmol/L), and time below range (TBR) (<3.9 mmol/L and <3.0 mmol/L) were assessed during three CGM time periods (switch [weeks 0–4], end of treatment [weeks 22–26], and follow-up [weeks 27–31]) for icodec versus comparators (ONWARDS 2, insulin degludec [basal regimen]; ONWARDS 4, insulin glargine U100 [basal-bolus regimen]) using double-blind CGM data. CGM-derived hypoglycemic episode duration (<3.9 mmol/L) was assessed. RESULTS: In both trials, there were no statistically significant differences in TIR, TAR, or TBR (<3.0 mmol/L) for icodec versus comparators across all time periods. In the end-of-treatment period, mean TIR was 63.1% (icodec) vs. 59.5% (degludec) in ONWARDS 2 and 66.9% (icodec) vs. 66.4% (glargine U100) in ONWARDS 4. Mean TBR <3.9 mmol/L and <3.0 mmol/L remained within recommended targets (<4% and <1%, respectively) across time periods and treatment arms. Hypoglycemic episode duration (<3.9 mmol/L) was comparable across time periods and treatment arms (median duration ≤40 min). CONCLUSIONS: In insulin-experienced participants with long-standing type 2 diabetes, CGM-based TIR, TAR, and CGM-derived hypoglycemia duration (<3.9 mmol/L) were comparable for icodec and once-daily basal insulin analogs during all time periods. TBR remained within recommended targets. [ABSTRACT FROM AUTHOR]

Aims: To evaluate gastrointestinal adverse events (AEs) and the impact of nausea, vomiting or diarrhoea (N/V/D) and any gastrointestinal (GI) AEs overall on weight change with tirzepatide across the SURPASS‐1 to ‐5 clinical trials. Materials and Methods: Participants with type 2 diabetes were randomized to receive once‐weekly tirzepatide (5, 10 or 15 mg) or comparator (placebo, semaglutide 1 mg once weekly, or titrated daily basal insulins) as monotherapy or added on to background antihyperglycaemic medication(s). This post hoc analysis subdivided participants within each trial into subgroups that self‐reported (yes/no) any N/V/D or GI AEs. Change from baseline in body weight at the primary timepoint was assessed within each trial and subgroup. Mediation analyses were conducted to evaluate the contribution of direct and indirect (mediated by N/V/D or GI AEs) effects of tirzepatide on weight change versus comparators. Results: Across the SURPASS‐1 to ‐5 trials (N = 6263), nausea (12%‐24%), diarrhoea (12%‐22%), and vomiting (2%‐13%) were the most common GI AEs reported with tirzepatide; these were transient and of mild‐to‐moderate severity. Mean weight reduction at the primary timepoint with tirzepatide was consistent between participants who reported N/V/D (−6.2 to −14.9 kg) and those who did not report N/V/D (−6.2 to −13.3 kg). Mean weight reduction was significantly (P < 0.01) greater with tirzepatide compared with placebo, semaglutide 1 mg, and basal insulins within the N/V/D and GI AEs subgroups. Mediation analyses suggested minimal contribution (<6%) of N/V/D and GI AEs to the overall difference in weight change between tirzepatide and comparators. Conclusions: Superior weight reduction with tirzepatide versus comparators appears to be independent of reported N/V/D or GI AEs. [ABSTRACT FROM AUTHOR]

Aim: To describe the phase 3a ONWARDS clinical development programme investigating insulin icodec (icodec), a once‐weekly basal insulin, including the design and rationale for each of the ONWARDS 1–6 trials. Materials and Methods: Six randomized controlled trials have been initiated in adults with type 2 diabetes (T2D) (insulin‐naive: ONWARDS 1, 3 and 5; previously insulin‐treated: ONWARDS 2 and 4) and type 1 diabetes (T1D) (ONWARDS 6). Each trial will investigate icodec use in a unique clinical scenario, with consideration of long‐term safety and varied comparator treatments (insulin glargine U100 or U300 or insulin degludec). ONWARDS 5 will incorporate real‐world elements and a digital dose titration solution to guide icodec dosing. The primary objective for each of the trials is to compare the change in HbA1c from baseline to week 26 or week 52 between icodec and comparator arms. Secondary objectives include investigating other glycaemic control and safety parameters, such as fasting glucose, time in glycaemic range and hypoglycaemia. Patient‐reported outcomes will assess treatment satisfaction. Conclusions: The ONWARDS 1–6 trials will evaluate the efficacy and safety of once‐weekly icodec compared with currently available daily basal insulin analogues in T2D and T1D. These trials will generate comprehensive evidence of icodec use in diverse populations across the spectrum of diabetes progression and treatment experience. [ABSTRACT FROM AUTHOR]