title: The effect of linagliptin on glycaemic control and tolerability in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Linagliptin is a new dipeptidyl peptidase-4 inhibitor recently approved for use in the USA. The objective of this systematic review and meta-analysis was to assess effect of linagliptin on glycaemic control, biomarkers and incidence of adverse events (AEs) in patients with type 2 diabetes mellitus.
  
  
  METHODS
  Five published and four unpublished randomized, clinical trials were identified from multiple databases. Qualitative assessments and quantitative analyses were performed.
  
  
  RESULTS
  Nine studies included 4246 participants with 53% men, 59.4% Caucasians, 38.7% Asians, and age range 45-69 years. Linagliptin was given as monotherapy (vs. placebo) or combined with metformin (vs. metformin + placebo), sulphonylurea (vs. sulphonylurea + placebo) or pioglitazone (vs. pioglitazone + placebo). Linagliptin 5 mg/day for 12-24 weeks, significantly reduced haemoglobin A1c (HbA1c) (-0.63%, p < 0.00001), fasting plasma glucose (FPG) (-1.01 mmol/l, p < 0.00001) and improved disposition index (DI, product of insulin sensitivity and acute insulin secretion) (p = 0.0001). Linagliptin monotherapy was not more effective than metformin at reducing HbA1c or FPG. Similar proportion of patients in linagliptin and placebo groups reported AEs including upper respiratory tract infections, headaches, nausea, hypertension and back pain.
  
  
  CONCLUSIONS
  Linagliptin was associated with modest but significant reduction in HbA1c and FPG and improved DI after 12-24 weeks. Patients who would probably benefit most are those with HbA1c <9%, already on an active agent, compliant with weight reduction strategies, and can recognize and manage hypoglycaemia, fluid retention and upper respiratory tract infections. Long-term studies are needed to determine durability of response, incidence of microvascular and macrovacular complications, cost-effectiveness and safety.
authors.affiliation: Pharmacy Practice, Nova Southeastern University, College of Pharmacy, FL 33324, USA. singh@nova.edu
authors.forename: D
authors.initials: D
authors.lastname: Singh-Franco
authors.forename: J
authors.initials: J
authors.lastname: McLaughlin-Middlekauff
authors.forename: S
authors.initials: S
authors.lastname: Elrod
authors.forename: C
authors.initials: C
authors.lastname: Harrington
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D003362:Cost-Benefit Analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D000069476:Linagliptin; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D000077205:Pioglitazone; D011687:Purines / Q000008:administration & dosage*; D011799:Quinazolines / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D045162:Thiazolidinediones / Q000008:administration & dosage*; D016896:Treatment Outcome; D014481:United States
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069476:Linagliptin; D008687:Metformin; D000077205:Pioglitazone; D011687:Purines; D011799:Quinazolines; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human