Summary Aims:  To compare the incidence of symptomatic hypoglycaemia in fasting Muslim patients with type 2 diabetes treated with sitagliptin or a sulphonylurea during Ramadan. Methods:  Patients with type 2 diabetes (age ≥ 18 years) who were treated with a stable dose of a sulphonylurea with or without metformin for at least 3 months prior to screening, who had an HbA1c < 10% and who expressed their intention to daytime fast during Ramadan were eligible for this open‐label study. Patients were randomised in a 1 : 1 ratio to either switch to sitagliptin 100 mg qd or to remain on their prestudy sulphonylurea. Patients completed daily diary cards to document information on hypoglycaemic symptoms and complications. The primary end‐point was the overall incidence of symptomatic hypoglycaemia recorded during Ramadan. Results:  Of the 1066 patients randomised, 1021 (n = 507 for sitagliptin and n = 514 for sulphonylurea) returned at least one completed diary card and were included in the analysis. The proportion of patients who recorded one or more symptomatic hypoglycaemic events during Ramadan was lower in the sitagliptin group (6.7%) compared with the sulphonylurea group (13.2%). The risk of symptomatic hypoglycaemia was significantly decreased with sitagliptin relative to sulphonylurea treatment (Mantel–Haenszel relative risk ratio [95% CI] = 0.51 [0.34, 0.75]; p < 0.001). There were no reported events that required medical assistance (i.e. visits to physician or emergency room or hospitalisations) or were considered severe (i.e. events that caused loss of consciousness, seizure, coma or physical injury) during Ramadan. Conclusions:  In Muslim patients with type 2 diabetes who observed the fast during Ramadan, switching to a sitagliptin‐based regimen decreased the risk of hypoglycaemia compared with remaining on a sulphonylurea‐based regimen. The incidence of hypoglycaemia was lower with gliclazide relative to the other sulphonylurea agents and similar to that observed with sitagliptin.

Objective: To directly compare the efficacy and safety of a fixed-ratio combination, iGlarLixi, with a premix insulin analog (BIAsp 30) as treatment advancement in type 2 diabetes suboptimally controlled on basal insulin plus oral antihyperglycemic drugs (OADs). ResearchDesign and Methods: SoliMix, a 26-week, open-label, multicenter study, randomized adults with suboptimally controlled basal insulin-treated type 2 diabetes (HbA 1c ≥7.5 % and ≤10 %) to once-daily iGlarLixi or twice-daily BIAsp 30. Primary efficacy endpoints were non-inferiority in HbA 1c reduction (margin 0.3 %) or superiority in bodyweight change for iGlarLixi versus BIAsp 30. Results: Both primary efficacy endpoints were met: after 26 weeks, baseline HbA 1c (8.6 %) was reduced by 1.3 % with iGlarLixi and 1.1 % with BIAsp 30, meeting non-inferiority (least squares [LS] mean difference [97.5% CI]: -0.2 [-0.4, -0.1] %; p<0.001). iGlarLixi was also superior to BIAsp 30 for bodyweight change (LS mean difference [95% CI] -1.9 [-2.3, -1.4] kg) and percentage of participants achieving HbA 1c <7 % without weight gain and HbA 1c <7 % without weight gain and without hypoglycemia (all p<0.001). iGlarLixi was also superior versus BIAsp 30 for HbA 1c reduction (p<0.001). Incidence and rates of ADA Level 1 and 2 hypoglycemia were lower with iGlarLixi versus BIAsp 30.Conclusions: Once-daily iGlarLixi provided better glycemic control with weight benefit and less hypoglycemia than twice-daily premix BIAsp 30. iGlarLixi is a more efficacious, simpler, and well-tolerated alternative to premix BIAsp 30 in suboptimally controlled type 2 diabetes requiring treatment beyond basal insulin plus OAD therapy.

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Aim Premix insulin is commonly used in some regions of the world, despite the higher risk of hypoglycaemia and weight gain compared with basal insulin, based on the premise that it offers a simplified insulin regimen. iGlarLixi is a once‐daily titratable fixed‐ratio formulation that combines basal insulin glargine 100 units/mL (iGlar) and the GLP‐1 RA, lixisenatide, which offers a single‐injection option for treatment intensification, with improved HbA1c reductions, similar hypoglycaemia risk and more favourable bodyweight profiles over iGlar alone. This randomized controlled study directly compares, for the first time, treatment intensification with iGlarLixi versus premix insulin analogue biphasic insulin aspart 30 (BIAsp 30) in adults with T2D inadequately controlled on basal insulin in combination with one or two oral antihyperglycaemic drugs. Materials and Methods This was an open‐label, active‐controlled, comparative, parallel‐group, multicentre, phase 3b study. In total, 887 adults with T2D uncontrolled on basal insulin were randomized to switch to either iGlarLixi once daily, or BIAsp 30 twice daily, for 26 weeks. Results Overall, 887 participants were enrolled (mean age 59.8 years, 50.2% female) from 89 centres in 17 countries. At baseline, 65.6% had a duration of T2D of 10 years or longer, and the mean HbA1c at baseline was 8.6%. Conclusions The study directly compared the efficacy and safety of iGlarLixi versus BIAsp 30 in people with T2D uncontrolled on basal insulin and one or more oral antihyperglycaemic agents. These results provide robust clinical data that may inform clinicians in their therapeutic management of people with T2D uncontrolled on basal insulin requiring additional therapy.

This study shows that hypoglycaemia has a significant but variable impact on the economics of diabetes healthcare globally.