Comparison of Oral Antidiabetic Drugs as Add-On Treatments in Patients with Type 2 Diabetes Uncontrolled on Metformin: A Network Meta-Analysis

Abstract

We assessed the efficacy and safety of oral antidiabetic drugs (OADs) as an add-on treatment in patients with type 2 diabetes uncontrolled on metformin. PubMed, the Cochrane Library, and Embase were searched from inception to October 20, 2017. Pairwise and network meta-analyses were conducted using Stata 14.1 software. Odds ratios (ORs) and weighted mean differences (WMDs) were used to evaluate outcomes. Sixty-eight trials including 36,746 patients were analyzed. No significant differences in the risk of major adverse cardiovascular events (MACEs) and all-cause mortality were observed among any class of OADs when combined with metformin. All classes of OADs as add-ons to metformin improved glucose control, while sodium-glucose co-transporter-2 (SGLT-2) inhibitors showed greater fasting plasma glucose (FPG) reductions {WMD, − 1.49 [95% confidence interval (CI) − 1.69 to − 1.28] mmol/l} and 2 h postprandial glucose (2 h PPG) reductions [WMD, − 3.07 (95% CI − 4.12 to − 2.03) mmol/l]. Thiazolidinediones and sulfonylureas were associated with weight gain [WMD, 2.53 (95% CI 1.95–3.10) kg and 2.00 (95% CI 1.63–2.36) kg, respectively] when added to metformin. Sulfonylureas [WMD, 6.52 (95% CI 4.07–10.45)] were associated with the highest ORs of hypoglycemia. Our results suggest that the seven classes of OADs were not associated with any increased risk of MACEs or all-cause mortality when combined with metformin. Most OADs were associated with similarly large reductions in HbA1c levels when added to metformin, while SGLT-2 inhibitors might be the best option for reducing body weight, FPG, and 2-h PPG.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0482-5) contains supplementary material, which is available to authorized users.

Management of Type 2 Diabetes in Developing Countries: Balancing Optimal Glycaemic Control and Outcomes with Affordability and Accessibility to Treatment

“…Concerns regarding sulfonylureas and cardiovascular complications have been addressed by a number of studies showing no difference in the risk of major adverse cardiovascular events or all-cause mortality between second-generation sulfonylureas and other classes of oral glucose-lowering agents [14,38,48,49]. The ADVANCE trial found that, compared to standard control, intensification of gliclazide modified release (MR) treatment was associated with long-term benefits on microvascular end points (new or worsening nephropathy and new or worsening retinopathy) in addition to effective glycaemic control [25].…”

Diabetes Care During Hajj

“… Metformin is associated with low rates of hypoglycaemia when compared with other oral therapies and is thus preferred during Hajj as long as it is well tolerated by the patient and the glomerular filtration rate is > 30 mL/min/1.73 m 2 [ 47 ]. In the absence of contraindications, sodium-glucose co-transporter-2 SGLT2 inhibitors can be used in combination with metformin to further reduce the risk of hypoglycaemia [ 44 ].…”

“…Metformin is associated with low rates of hypoglycaemia when compared with other oral therapies and is thus preferred during Hajj as long as it is well tolerated by the patient and the glomerular filtration rate is > 30 mL/min/1.73 m 2 [ 47 ].…”

rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study

“…Since monotherapy may fail to achieve its goal in reaching glycemic control in individuals with T2DM [ 5 ], combination therapy is usually required and should involve agents with different and complementary mechanisms of action [ 6 ]. Recent studies show that early combination therapies were associated with better glycemic control [ 7 ].…”