Comparison of antidiabetic drugs added to sulfonylurea monotherapy in patients with type 2 diabetes mellitus: A network meta-analysis

Abstract

Aims: This study aimed to investigate the efficacy and safety of dual therapy comprising sulfonylurea (SU) plus antidiabetic drugs for the treatment of type 2 diabetes mellitus (T2DM).

Methods: We searched the PubMed, Cochrane library, and Embase databases for randomized clinical trials (≥24 weeks) published up to December 28, 2017. Subsequently, we conducted pairwise and network meta-analyses to calculate the odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) of the outcomes.

Results: The final analyses included 24 trials with a total of 10,032 patients. Compared with placebo, all treatment regimens were associated with a significantly higher risk of hypoglycemia, except the combinations of SU plus sodium-glucose co-transporter-2 inhibitor (SGLT-2i) [OR, 1.35 (95% CI: 0.81 to 2.25)] or alpha-glucosidase inhibitor (AGI) [OR, 1.16 (95% CI: 0.55 to 2.44)]. Notably, the combination of SU plus glucagon-like peptide-1 receptor agonist (GLP-1RA) was associated with the most significant increase in the risk of hypoglycemia. Furthermore, all SU-based combination regimens reduced the glycated hemoglobin (HbA1c) and fasting plasma glucose levels (FPG). However, only combinations containing SGLT-2i [MD, -1.00 kg (95% CI: -1.73 to -0.27)] and GLP-1RA [MD, -0.56 kg (95% CI: -1.10 to -0.02)] led to weight loss.

Conclusions: Our findings highlight the importance of considering the risk of hypoglycemia when selecting antidiabetic drugs to be administered concomitantly with SU. Although all classes of antidiabetic drugs improved glucose control when administered in combination with SU, SGLT-2i might be the best option with respect to factors such as hypoglycemia and body weight.

Fig 1. Flow chart of the search for eligible studies.

Fig 2. Network maps for efficacy and safety outcomes.

Note: Connecting lines represent direct comparisons between the pairs of treatments, and the line widths represent the numbers of trials. The node sizes represent the overall sample sizes of the interventions. HbA1c, glycated hemoglobin; FPG, fasting plasma glucose; SGLT-2i, sodium-glucose co-transporter-2 inhibitor; DPP-4i, dipeptidyl peptidase-4 inhibitor; GLP-1RA, glucagon-like peptide-1 receptor agonist; TZD, thiazolidinedione; Met, metformin; AGI, α-glucosidase inhibitor; Basal, basal (long-acting) insulin.

Fig 3. Differences versus placebo in efficacy and safety outcomes.

Note: HbA1c, glycated hemoglobin; FPG, fasting plasma glucose; SGLT-2i, sodium-glucose co-transporter-2 inhibitor; DPP-4i, dipeptidyl peptidase-4 inhibitor; GLP-1RA, glucagon-like peptide-1 receptor agonist; TZD, thiazolidinedione; Met, metformin; AGI, α-glucosidase inhibitor; Basal, basal (long-acting) insulin.