Efficacy and safety of glucose-lowering agents in patients with type 2 diabetes: A network meta-analysis of randomized, active comparator-controlled trials

• Published in: Nutrition, metabolism, and cardiovascular diseases metabolism, and cardiovascular diseases, 2021-04, Vol.31 (4), p.1027-1034
• Main Authors: Mannucci, Edoardo, Naletto, Lara, Vaccaro, Gabriele, Silverii, Antonio, Dicembrini, Ilaria, Pintaudi, Basilio, Monami, Matteo
• Format: Article
• Language: English
• Subjects: Aged; Biomarkers - blood; Blood Glucose - drug effects; Blood Glucose - metabolism; Body Weight - drug effects; Clinical Decision-Making; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - drug therapy; Female; Gastrointestinal Diseases - chemically induced; Humans; Hypoglycemia - chemically induced; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Incretin therapy; Insulin therapy; Male; Middle Aged; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic; SGLT2 inhibitor; Thiazolidinediones; Treatment Outcome; Type 2 diabetes
• ISSN: 0939-4753; 1590-3729
• DOI: 10.1016/j.numecd.2020.12.030

Aim of the present network meta-analysis (NMA) is the comparison across glucose-lowering drugs (GLA) concerning their effects on glucose control, body weight, hypoglycemia, gastrointestinal adverse events, and quality of life. This NMA includes randomized clinical trials comparing different head-to-head comparison trials with EMA-approved GLA in type 2 diabetes, with a duration of ≥52 weeks. All drugs have to be administered at the maximal approved dose. Primary endpoints were HbA1c at 12, 52, and 104+ weeks. Secondary endpoints were body weight, quality of life, hypoglycemia, and gastrointestinal disorders. Indirect comparisons of different GLA were performed by NMA choosing metformin as reference. The standardized difference in means (SDM) and Mantel-Haenzel Odds Ratio [MH–OR] (using random-effect models) with 95% Confidence Intervals were calculated for categorical and continuous variables, respectively. We included 68 trials fulfilling all inclusion criteria. At 12 weeks, when considering indirect comparisons, insulin secretagogues (IS) were associated with a significantly greater reduction in comparison with metformin (SDM, −0.3 [-0.4;-0.2]%); a significantly lower efficacy was observed for pioglitazone. At 52 weeks, IS were no longer associated with a greater reduction of HbA1c; whereas a significant decrease in HbA1c was observed for GLP-1 RA (SDM, −0.2 [-0.1;-0.3]%). At 104+ weeks, only SGLT-2 inhibitors showed a significantly greater HbA1c reduction (SDM, −0.2 [-0.1;-0.3]%), whereas sulfonylureas and insulin showed a significantly lower efficacy (SDM, 0.1 [0.0; 0.2]%), and 0.4 [0.3; 0.5]%, respectively). The results of this meta-analysis should be considered together with evidence on long-term outcomes for selecting the most appropriate drugs for individual patients. •Different classes of drugs have different effects on glucose control depending to the length of treatment.•Sulfonylureas were effective drugs in the short term, but less effective when increasing the duration of treatment.•SGLT2 inhibitors and GLP-1 RA were the most effective drugs in the longer term.