title: 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.
abstract: OBJECTIVE
  To determine which non-insulin glucose-lowering treatment regimens are most appropriate in people with type 2 diabetes who choose to fast during Ramadan.
  
  
  METHODS
  Electronic databases were searched for randomized controlled trials (RCTs) and observational studies that compared non-insulin glucose-lowering agents in people with type 2 diabetes fasting during Ramadan. Those studies which reported hypoglycaemia, weight and glycated haemoglobin (HbA1c) change were included. Data were pooled using random effects models.
  
  
  RESULTS
  A total of 16 studies were included: 9 RCTs and 7 observational studies. There was evidence that dipeptidyl peptidase-4 (DPP-4) inhibitors led to fewer hypoglycaemic events compared with sulphonylureas. Sitagliptin significantly reduced the number of patients with ≥1 hypoglycaemic episodes during Ramadan [risk ratio (RR) 0.48, 95% confidence interval (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 (I(2)  = 86.7%). Significant reductions in HbA1c and weight were seen in the observational studies of vildagliptin versus sulphonylureas. The use of liraglutide led to significant weight loss (-1.81 kg, 95% CI -2.91, -0.71; p = 0.001) compared with sulphonylureas. Pioglitazone significantly increased weight compared with placebo (3.48 kg, 95% CI 2.82, 4.14; p < 0.0001).
  
  
  CONCLUSIONS
  The analysis supports the use of DPP-4 inhibitors during Ramadan rather than sulphonylureas for reduction in hypoglycaemia without a cost to diabetes control and weight. The glucagon-like peptide (GLP)-1 agonist liraglutide provides clinical benefits, but more studies are required. RCTs of DPP-4 inhibitors compared with GLP-1 agonists and novel therapies including the sodium-glucose co-transporter 2 and α-glucosidase inhibitors are needed to inform evidence-based guidelines.
authors.affiliation: Department of Health Sciences, University of Leicester, Leicester, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Gray
authors.affiliation: Diabetes Research Centre, University of Leicester, Leicester, UK.
authors.forename: J
authors.initials: J
authors.lastname: Dales
authors.affiliation: Leicester Diabetes Centre, University Hospitals of Leicester, Leicester, UK.
authors.forename: E M
authors.initials: EM
authors.lastname: Brady
authors.affiliation: Diabetes Research Centre, University of Leicester, Leicester, UK.|Leicester Diabetes Centre, University Hospitals of Leicester, Leicester, UK.
authors.forename: K
authors.initials: K
authors.lastname: Khunti
authors.affiliation: Department of Diabetes & Endocrinology, University Hospital Birmingham, NHS Trust, Birmingham, UK.
authors.forename: W
authors.initials: W
authors.lastname: Hanif
authors.affiliation: Diabetes Research Centre, University of Leicester, Leicester, UK.|Leicester Diabetes Centre, University Hospitals of Leicester, Leicester, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Davies
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000187:drug effects; D006693:Holidays; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007514:Islam; D000069450:Liraglutide / Q000627:therapeutic use; D009570:Nitriles / Q000627:therapeutic use; D064887:Observational Studies as Topic; D000077205:Pioglitazone; D011759:Pyrrolidines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use; D000077597:Vildagliptin; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D009570:Nitriles; D000077205:Pioglitazone; D011759:Pyrrolidines; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D000077597:Vildagliptin; C517652:hemoglobin A1c protein, human
keywords: DPP-IV inhibitor; GLP-1 analogue; meta-analysis; sulphonylureas; systematic review; type 2 diabetes