The safety and effectiveness of non-insulin glucose lowering agents in the treatment of people with Type 2 Diabetes who observe Ramadan: A systematic review and meta-analysis

Aims: To determine which non-insulin glucose lowering treatment regimens are most appropriate in people with type 2 diabetes who choose to fast during Ramadan. Materials and methods: Electronic databases were searched for randomised controlled trials (RCT) and observational studies comparing non-insulin glucose lowering agents in people with type 2 diabetes fasting during Ramadan reporting hypoglycaemia, weight and HbA1c change were included. Data were pooled using random effects models. Results: Sixteen studies included; nine RCTs and seven observational studies. There was evidence that DPP-4 inhibitors led to less hypoglycaemic events compared to sulphonylureas. Sitagliptin significantly reduced the number of patients ≥1 hypoglycaemic episodes during Ramadan (RR 0.48, 95%CI 0.36, 0.64, p>0.0001), this was not replicated in the RCTs of vildagliptin but a significant reduction was found in the observational studies (RR 0.28, 95%CI 0.10, 0.75, p=0.01) with high heterogeneity (I2=86.7%). Significant reductions in HbA1c and weight were seen in the observational studies of vildagliptin vs. sulfonylureas. The use of liraglutide led to significant weight loss (-1.81kg, 95%CI -2.91, -0.71, p=0.001) compared to sulfonylureas. Pioglitazone significantly increased weight compared to placebo (3.48kg, 95%CI 2.82, 4.14, p<0.0001). Conclusions: The analysis supports the use of DPP-4 inhibitors during Ramadan over sulfonylureas for reduction in hypoglycaemic episodes without a cost to diabetes control and weight. The GLP-1 agonist liraglutide provides clinical benefits, but more studies are required. RCTs of DPP-4 inhibitors against GLP-1 agonists and novel therapies including the SGLT-2 and alpha-glucosidase inhibitors are needed to inform evidence based guidelines.