Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials.

AIMS/HYPOTHESIS: We conducted a systematic review and network meta-analysis to compare the efficacy and safety of s.c. administered tirzepatide vs s.c. administered semaglutide for adults of both sexes with type 2 diabetes mellitus. METHODS: We searched PubMed and Cochrane up to 11 November 2023 for RCTs with an intervention duration of at least 12 weeks assessing s.c. tirzepatide at maintenance doses of 5 mg, 10 mg or 15 mg once weekly, or s.c. semaglutide at maintenance doses of 0.5 mg, 1.0 mg or 2.0 mg once weekly, in adults with type 2 diabetes, regardless of background glucose-lowering treatment. Eligible trials compared any of the specified doses of tirzepatide and semaglutide against each other, placebo or other glucose-lowering drugs. Primary outcomes were changes in HbA1c and body weight from baseline. Secondary outcomes were achievement of HbA1c target of ≤48 mmol/mol (≤6.5%) or <53 mmol/mol (<7.0%), body weight loss of at least 10%, and safety outcomes including gastrointestinal adverse events and severe hypoglycaemia. We used version 2 of the Cochrane risk-of-bias tool (ROB 2) to assess the risk of bias, conducted frequentist random-effects network meta-analyses and evaluated confidence in effect estimates utilising the Confidence In Network Meta-Analysis (CINeMA) framework. RESULTS: A total of 28 trials with 23,622 participants (44.2% female) were included. Compared with placebo, tirzepatide 15 mg was the most efficacious treatment in reducing HbA1c (mean difference -21.61 mmol/mol [-1.96%]) followed by tirzepatide 10 mg (-20.19 mmol/mol [-1.84%]), semaglutide 2.0 mg (-17.74 mmol/mol [-1.59%]), tirzepatide 5 mg (-17.60 mmol/mol [-1.60%]), semaglutide 1.0 mg (-15.25 mmol/mol [-1.39%]) and semaglutide 0.5 mg (-12.00 mmol/mol [-1.09%]). In between-drug comparisons, all tirzepatide doses were comparable with semaglutide 2.0 mg and superior to semaglutide 1.0 mg and 0.5 mg. Compared with placebo, tirzepatide was more efficacious than semaglutide for reducing body weight, with reductions ranging from 9.57 kg (tirzepatide 15 mg) to 5.27 kg (tirzepatide 5 mg). Semaglutide had a less pronounced effect, with reductions ranging from 4.97 kg (semaglutide 2.0 mg) to 2.52 kg (semaglutide 0.5 mg). In between-drug comparisons, tirzepatide 15 mg, 10 mg and 5 mg demonstrated greater efficacy than semaglutide 2.0 mg, 1.0 mg and 0.5 mg, respectively. Both drugs increased incidence of gastrointestinal adverse events compared with placebo, while neither tirzepatide nor semaglutide increased the risk of serious adverse events or severe hypoglycaemia. CONCLUSIONS/INTERPRETATION: Our data show that s.c. tirzepatide had a more pronounced effect on HbA1c and weight reduction compared with s.c. semaglutide in people with type 2 diabetes. Both drugs, particularly higher doses of tirzepatide, increased gastrointestinal adverse events. REGISTRATION: PROSPERO registration no. CRD42022382594.

Efficacy and safety of faster aspart in insulin pumps in children and adolescents with type 1 diabetes mellitus: A single-center study with real-world data.

AIMS: To assess the efficacy and safety of faster aspart (FIAsp) in paediatric population with type 1 diabetes mellitus (T1DM) and insulin pumps in real-world settings. METHODS: Of 44 patients, 20 used FIAsp, 16 of which switched from aspart to FIAsp and 24 used aspart/lispro. We performed within-groups and between-groups analyses in three time points for anthropometric data, % of 24-h time in range of 70-180 mg/dl (TIR), time < 70 mg/dl and <54 mg/dl and time > 180 mg/dl and >250 mg/dl, bolus and basal insulins doses (units/kg/day and %), total daily dose (TDD, units/kg/day), glycaemic variability, frequency of set changes, sensor wear per week and meals per day. RESULTS: Use of FIAsp over time increased TIR (P = 0.002) and TDD (P = 0.008 and P = 0.004, respectively for three months after the switch and recent use) and decreased time in hyperglycaemia (>180 P = 0.003 and > 250 mg/dl, P = 0.004). Frequency of set changes differ in the first 3 months (P = 0.042). Patients with FIAsp consumed more meals per day compared to those with aspart/lispro (P = 0.032). CONCLUSION: Real-world data confirm that use of FIAsp in insulin pumps in paediatric populations improves glycaemic control long-term.

Puberty in boys with type 1 diabetes mellitus: What has changed?

AIMS: To study the age of pubertal onset and secular trend in boys with Type 1 diabetes mellitus (T1DM) followed in two centers in North Greece. METHODS: Boys with T1DM visited the Outpatient Clinics of the 1st and 2nd Department of Paediatrics of Aristotle University of Thessaloniki from March until June 2022 were enrolled. Recent anthropometric data were recorded during the follow-up visit whereas previous anthropometric data and demographic data were collected from medical files. A volume of testis > 3 ml was indicative for the onset of puberty. RESULTS: A total of 46 boys with T1DM with documented pubertal onset after the diagnosis of T1DM were included in the study. Precocious puberty (<9 years old) was recorded in 5 boys (10.2 %), early puberty (<10 years but >9 years) in 10 (20.4 %) and 34 (69.4 %) entered puberty normally. The duration of T1DM was inversely correlated to the likelihood of earlier puberty (P < 0.001). However, no notable year predominance was observed suggesting no COVID-19 effect. CONCLUSION: A considerable number of Greek boys with T1DM appear to develop precocious and early puberty, raising thoughts regarding diabetes management and other possible cofactors.

Efficacy and safety of ultra-rapid insulin analogues in insulin pumps in patients with Type 1 Diabetes Mellitus: A systematic review and meta-analysis.

AIMS: To assess the efficacy and safety of ultra-rapid insulin analogues used with continuous subcutaneous insulin infusion systems (CSII) in adults with type 1 diabetes (T1DM). METHODS: We searched MEDLINE and Cochrane Library up to May 2022 for randomized controlled trials comparing ultra-rapid with rapid-acting insulin analogues (RAIAs) used with CSII. We performed random effects meta-analyses for % of 24-h time in range of 70-180 mg/dl (TIR), time in hypoglycaemia (<70 mg/dl) and hyperglycaemia (>180 mg/dl), 1- and 2-hour post-prandial glucose [PPG] increment after a meal test, HbA1c and average insulin dose at endpoint, unplanned infusion set changes and severe hypoglycaemia. RESULTS: Nine studies (1,156 participants) were included. Ultra-rapid insulins were superior to RAIAs on TIR (mean difference [MD] 1.1 %, 95 % CI 0.11-2.11), time spent in hypoglycaemia (MD -0.47 %, 95 % CI -0.63 to -30), and 1- and 2-hour PPG (MD -12.20 mg/dl, 95 % CI -19.85 to -4.54 and MD -17.61 mg/dl, 95 % CI -28.55 to -6.66, respectively). Ultra-rapid insulins increased odds of unplanned infusion set changes (odds ratio 1.60, 95 % CI 1.26-2.03). CONCLUSION: Ultra-rapid acting insulins provided better PPG control compared to RAIAs but their use might result in more infusion set changes.