Efficacy and Safety of Once-weekly Semaglutide S.C. 2.0 mg as Add-on to Dose-reduced Insulin Glargine vs Titrated Insulin Glargine in Participants With Type 2 Diabetes and Overweight
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 573
- 试验地点
- 386
- 主要终点
- Change in Glycated Haemoglobin (HbA1c)
研究概览
简要总结
This study compares semaglutide, together with a lower dose of insulin glargine, to a higher dose of insulin glargine in participants with type 2 diabetes. The study looks at how well the study medicines control blood glucose levels. Participants will either get semaglutide together with a lower dose of insulin glargine or a higher dose of insulin glargine. The study will last for about 47 weeks (approximately 11 months). Participants will have 9 clinic visits, 15 phone/video calls and 1 home visit. Participants will be asked to wear a sensor that measures their blood sugar all the time in 2 periods of 10 days during the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with Type 2 Diabetes Mellitus (T2D) mellitus greater than or equal to (>=) 180 days before screening.
- •Glycated haemoglobin (HbA1c) of 7-10 percentage [(53-86 millimoles per mole (mmol/mol)] (both inclusive) as assessed by central laboratory on the day of screening.
- •Body mass index (BMI) greater than or equal to (>=) 25 kilograms per meter square (kg/m^2) on the day of screening.
- •Stable daily dose(s) greater than or equal to (>=) 90 days before screening of any of the following anti-diabetic drugs or combination regimens:
- •Any metformin formulations greater than or equal to (>=) 1500 milligrams (mg) or maximum tolerated or effective dose.
- •Any metformin combination formulation greater than or equal to (>=) 1500 mg or maximum tolerated or effective dose.
- •The treatment can be with or without sodium glucose cotransporter 2 (SGLT-2) inhibitors.
- •Treated with a once daily basal insulin (e.g. insulin glargine Unit 100 or U300, neutral protamine hagedorn (NPH) insulin, insulin detemir, insulin degludec) less than or equal to (<=) 40 units/day (U/day) for greater than or equal to (>=) 90 days before screening. Short-term bolus insulin treatment for a maximum of 14 days before screening is allowed.
排除标准
- •Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
- •Potentially missed diagnosis of Type 1 diabetes (T1D) or latent autoimmune diabetes in adults (LADA) verified by C-peptide less than 0.26 nanomoles per litre (nmol/L) (or 260 picomoles per liter [pmol/L] [0.78 nanograms per millilitre {ng/mL}]) or antibodies to glutamic acid decarboxylase (anti-GAD) greater than 5 units/millilitre, as measured by the central laboratory at screening.
- •Presence or history of pancreatitis (acute or chronic).
- •Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of less than 30 millilitre per minute per 1.73 meter square at screening as defined by Kidney Disease: Improving Global Outcomes (KDIGO) 2012 classification.
- •Any episodes of diabetic ketoacidosis within 90 days before screening.
- •Known hypoglycaemic unawareness as indicated by the investigator according to Clarke's questionnaire question 8.
研究组 & 干预措施
Insuline glargine U100 (titrated)
Participants will receive titrated insuline glargine U100 s.c. once-daily. Insulin glargine U100 dose will be adjusted based on the mean of three pre-breakfast SMPG values (target SMPG: 4.4-7.2 mmol/L).
干预措施: Insuline glargine U100 (titrated) (Drug)
Insuline glargine U100 (reduced) + semaglutide
Participants will initially receive 0.25 milligrams (mg) once-weekly semaglutide subcutaneously (s.c.) and the dose will be gradually escalated to 2 mg as an add-on to dose-reduced insulin glargine s.c. given once-daily. Insulin glargine U100 will be reduced by 10 U at the initiation of semaglutide and then again at each semaglutide dose escalation. Insulin glargine dose will be adjusted based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values (target SMPG: 4.4-7.2 millimoles per litre (mmol/L)).
干预措施: Semaglutide (Drug)
Insuline glargine U100 (reduced) + semaglutide
Participants will initially receive 0.25 milligrams (mg) once-weekly semaglutide subcutaneously (s.c.) and the dose will be gradually escalated to 2 mg as an add-on to dose-reduced insulin glargine s.c. given once-daily. Insulin glargine U100 will be reduced by 10 U at the initiation of semaglutide and then again at each semaglutide dose escalation. Insulin glargine dose will be adjusted based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values (target SMPG: 4.4-7.2 millimoles per litre (mmol/L)).
干预措施: Insuline glargine U100 (reduced) (Drug)
结局指标
主要结局
Change in Glycated Haemoglobin (HbA1c)
时间窗: From baseline (week 0) to end of treatment (week 40)
Non-inferiority of semaglutide s.c. as add-on to dose-reduced insulin glargine to that of titrated insulin glargine will be assessed based on the clinically acceptable margin of 0.3 percentage (%) for the mean treatment difference in HbA1c. Measured as percentage.
次要结局
- Relative Change in Daily Insulin Dose(From baseline (week 0) to end of treatment (week 40))
- Participants Achieving: Insulin Dose Reduced From Baseline by at Least 50 Percentage (Yes/No)(At end of treatment (week 40))
- Participants Achieving: Insulin Dose Equal to 0 Units (Yes/No)(At end of treatment (week 40))
- Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by Blood Glucose Meter) or Severe Hypoglycaemic Episodes (Level 3)(From baseline (week 0) to end of treatment (week 40))
- Participants Achieving All of The Following Targets: HbA1c Reduced From Baseline by At Least 0.3 %; Insulin Dose Reduced From Baseline; No Hypoglycaemic Episodes; No Weight Gain(At end of treatment (week 40))
- Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 Millimoles Per Litre (mmol/L) [54 Milligrams Per Decilitre (mg/dL)] Confirmed by Blood Glucose Meter)(From baseline (week 0) to end of treatment (week 40))
- Change in HbA1c(From baseline (week 0) to end of treatment (week 40))
- Participants Achieving: HbA1c less than 7 Percentage (Yes/No)(At end of treatment (week 40))
- Change in Score of Diabetes Treatment Satisfaction Questionnaire - Status Version (DTSQs)(From baseline (week 0) to end of treatment (week 40))
- Change in Body Weight(From baseline (week 0) to end of treatment (week 40))
- Score of Diabetes Treatment Satisfaction Questionnaire - Change Version (DTSQc)(At end of treatment (week 40))
- Number of Severe Hypoglycaemic Episodes (Level 3)(From baseline (week 0) to end of treatment (week 40))
- Change in Score of Short Form 36 Version 2 (SF-36 v2)(From baseline (week 0) to end of treatment (week 40))