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Efficacy and Safety of Once-Weekly Semaglutide 2.0 mg as an Add-On to Dose-Reduced Insulin Glargine versus Dose-Titrated Insulin Glargine in People With Type 2 Diabetes and Overweight (SUSTAIN OPTIMIZE).

Helena W Rodbard·Concetta Irace·Jevitha Lobo·Konstantinos Makrilakis·Prachi Priyadarshini·Suvanjaa Sivalingam·Santiago Tofé Povedano·Anuj Bhargava
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Abstract

AIMS: Type 2 diabetes (T2D) management with basal insulin can lead to hypoglycaemia and weight gain. SUSTAIN OPTIMIZE compared once-weekly semaglutide 2.0&#x2009;mg as add-on to dose-reduced insulin glargine (Sema+IGlarreduced) versus dose-titrated IGlar (IGlartitrated) on glycated haemoglobin (HbA1c), body weight (BW), daily insulin dose, and participant satisfaction. MATERIALS AND METHODS: SUSTAIN OPTIMIZE was a 40-week, phase 3b, open-label, randomised study. Adults with T2D, overweight (body mass index &#x2265;&#x2009;25&#x2009;kg/m2), and treatment with basal insulin &#x2264;&#x2009;40&#x2009;units/day were randomised 1:1 into Sema+IGlarreduced or IGlartitrated. The primary endpoint was change in HbA1c using a non-inferiority approach. Secondary endpoints assessed superiority of Sema+IGlarreduced versus IGlartitrated in reducing HbA1c, BW, daily insulin dose, and improving Diabetes Treatment Satisfaction Questionnaire change version (DTSQc) scores. RESULTS: Overall, 573 participants were randomised. Sema+IGlarreduced achieved both non-inferiority and superiority versus IGlartitrated in HbA1c reduction (estimated treatment difference [ETD]: -0.74%; 95% confidence interval [CI95]: -0.90, -0.59) and superiority in BW change (ETD: -8.5&#x2009;kg; CI95: -9.5, -7.4), relative daily insulin dose change (ETD: -121.9%; CI95: -143.1, -100.6), and DTSQc scores (ETD: 2.6; CI95: 1.6, 3.5) (p&#x2009;<&#x2009;0.0001 for all endpoints). No new safety concerns were identified. Severe hypoglycaemia was reduced (rate ratio: 0.45; CI95: 0.23, 0.87; p&#x2009;=&#x2009;0.02), while gastrointestinal events were higher for Sema+IGlarreduced (310 vs. 32 events). CONCLUSIONS: Once-weekly subcutaneous semaglutide 2.0&#x2009;mg as add-on to dose-reduced IGlar achieved superior reductions in HbA1c, BW, and daily insulin dose in people with T2D and overweight, while reducing their risk for severe hypoglycaemia compared to dose-titrated IGlar alone.

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AdultAgedFemaleHumansMaleMiddle AgedBlood GlucoseDiabetes Mellitus, Type 2Dose-Response Relationship, DrugDrug Administration ScheduleDrug Therapy, CombinationGlucagon-Like PeptidesGlycated HemoglobinHypoglycemiaHypoglycemic AgentsInsulin GlargineOverweightSemaglutideTreatment OutcomeGLP&#x2010;1clinical trialglycaemic controlhypoglycaemiainsulin glarginesemaglutideJournal ArticleRandomized Controlled TrialClinical Trial, Phase IIIMulticenter Study

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Helena W Rodbard, Concetta Irace, Jevitha Lobo, Konstantinos Makrilakis, Prachi Priyadarshini, Suvanjaa Sivalingam, Santiago Tof&#xe9; Povedano, Anuj Bhargava. 2026-07-26. Efficacy and Safety of Once-Weekly Semaglutide 2.0&#x2009;mg as an Add-On to Dose-Reduced Insulin Glargine versus Dose-Titrated Insulin Glargine in People With Type 2 Diabetes and Overweight (SUSTAIN OPTIMIZE).. https://doi.org/10.1111/dom.71132

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Adult subjectAged subjectBlood Glucose subjectClinical Trial subjectClinical Trial, Phase III subjectDiabetes Mellitus, Type 2 subjectDose-Response Relationship, Drug subjectDrug Therapy, Combination subjectFemale subjectHumans subjectJournal Article subjectMale subjectMiddle Aged subjectMulticenter Study subjectOverweight subjectRandomized controlled trials study

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