A meta-analysis 2 estimating the relative efficacy and safety associated with glucose-lowering drugs included 301 trials (1 417 367 patient-months). Compared with metformin, sulfonylurea (standardized mean difference [SMD] 0.18, 95% CI 0.01 to 0.34), thiazolidinedione (SMD 0.16, 95% CI, 0.00 to 0.31), DPP-4 inhibitor (SMD 0.33, 95% CI 0.13 to 0.52), and α-glucosidase inhibitor (SMD 0.35, 95% CI 0.12 to 0.58) monotherapy were associated with higher HbA1c levels.
A Cochrane review [Abstract] 1 included 32 studies with a total of 28 746 subjects with type 2 diabetes mellitus. Metformin and sulphonylurea (M+S) combination was compared with other antidiabetic medications. Treatment duration ranged between 1 to 4 years. There was no difference in all-cause and cardiovascular mortality, serious adverse events, non-fatal stroke, non-fatal myocardial infarction (MI) and microvascular complications. There were more mild or moderate hypoglycaemias in the sulphonylurea group (RR 5.60 (95% CI 2.38 to 13.14, n=3309).
A population based cohort 3 study using UK Clinical Practice Research Datalink assessed whether adding or switching to sulfonylureas was associated with an increased morbidity. Among 77 138 metformin initiators, 25 699 added or switched to sulfonylureas during the 5 year study period. During a mean follow-up of 1.1 years, sulfonylureas were associated with an increased risk of severe hypoglycaemia (5.5 v 0.7; HR 7.60, 95% CI 4.64 to 12.44) compared with continuing metformin monotherapy.
Another meta-analysis 4 assessing effects of metformin monotherapy on glycemic control and weight in drug-naive patients with type 2 diabetes included 16 studies (n=1140). Compared to placebo, metformin monotherapy was associated with decreased glycosated hemoglobin (HbA1c) by 0.95% at 3 months (95% CI 0.50 to 1.39; I²=87%) and 1.32% at 6 months (95% CI 1.01 to 1.62; I²=71%), and decreased fasting plasma glucose by 1.92mmol/L at 1 month (95% CI 0.11 to 3.74, I²=88%), 1.79mmol/L at 3 months (95% CI 0.92 to 2.66, I²=88%) and 2.14mmol/L at 6 months (95% CI 1.17 to 3.12; I²=82%). No significant difference was demonstrated for the comparisons of weight due to relatively small number of studies retrieved.
A network meta-analysis 5 included 39 RCTs involving 17 860 individuals. Glucagon-like peptide-1 (GLP-1) analogues resulted in greater decrease in HbA1c compared with sulfonylureas (-0.20% ,95% CI -0.34 to -0.04%), glinides (-0.31%, 95% CI -0.61 to -0.02%), thiazolidinediones (-0.20%, 95% CI -0.38 to -0.00), α-glucosidase inhibitors (-0.36%, 95% CI -0.64 to -0.07%), and DPP-4 inhibitors (-0.32%, 95% CI -0.47 to -0.17%). HbA1c decrease was greater for biphasic insulin compared with glinides (-0.36%; 95% CI -0.82 to -0.11%). Compared with placebo, the risk of hypoglycaemia was increased in the sulfonylureas, glinides, basal insulin and biphasic insulin. Weight increase was seen with sulfonylureas, glinides, thiazolidinediones, basal insulin and biphasic insulin.
A systematic review and meta-analysis 6 included 9 RCTs involving 10 974 participants assessing safety and efficacy of metformin-SGLT2i versus metformin-sulfonylureas.There was no significant difference in all-cause mortality (RR 0.93, 95% CI 0.52 to 1.67) and serious adverse events (RR 0.96, 95% CI 0.79 to 1.17) between the two, but in hypoglycemia (RR 0.13, 95% CI 0.10 to 0.17). Participants taking metformin-SGLT2i showed a significantly greater reduction in HbA1c (mean difference [MD] - 0.10%, 95% CI - 0.17 to - 0.03], body weight (MD - 4.57 kg, 95% CI - 4.74 to - 4.39), and fasting plasma glucose (MD - 0.55 mmol/L, 95% CI - 0.69 to - 0.41).
Date of latest search: 2024-01-04
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