Comparative effectiveness of incretin-based therapies and the risk of death and cardiovascular events in 38,233 metformin monotherapy users

John-Michael Gamble, Jamie M Thomas, Laurie K Twells, William K Midodzi, Sumit R Majumdar
Medicine (Baltimore) 2016, 95 (26): e3995
There is limited comparative effectiveness evidence to guide approaches to managing diabetes in individuals failing metformin monotherapy. Our aim was to compare the incidence of all-cause mortality and major adverse cardiovascular events (MACEs) among new metformin monotherapy users initiating a dipeptidyl-peptidase-4 inhibitor (DPP4i), glucagon-like peptide-1 receptor agonist (GLP-1RA), sulfonylurea (SU), thiazolidinedione, or insulin.We conducted a cohort study using the UK-based Clinical Practice Research Datalink. Participants included a cohort of 38,233 new users of metformin monotherapy who initiated a 2nd antidiabetic agent between January 1, 2007 and December 31, 2012 with follow-up until death, disenrollment, therapy discontinuation, or study end-date. A subcohort of 21,848 patients with linked hospital episode statistics (HES) and Office of National Statistics (ONS) data were studied to include MACE and cardiovascular-related death. The primary exposure contrasts, defined a priori, were initiation of a DPP4i versus an SU and initiation of a GLP-1RA versus an SU following metformin monotherapy. Cox proportional hazards models were used to assess the relative differences in time to mortality and MACE between exposure contrasts, adjusting for important baseline patient factors and comedications used during follow-up.The main study cohort consisted of 6213 (16%) patients who initiated a DPP4i, 25,916 initiated an SU (68%), 4437 (12%) initiated a TZD, 487 (1%) initiated a GLP-1RA, 804 (2%) initiated insulin, and 376 (1%) initiated a miscellaneous agent as their 2nd antidiabetic agent. Mean age was 62 years, 59% were male, and mean glycated hemoglobin was 8.8% (92.6 mmol/mol). Median follow-up was 2.7 years (interquartile range 1.3-4.2). Mortality rates were 8.2 deaths/1000 person-years for DPP4i and 19.1 deaths/1000 person-years for SU initiators. Adjusted hazards ratio (aHR) for mortality in DPP4i versus SU initiators = 0.58, 95% CI 0.46 to 0.73, P < 0.001. MACE rates were 19.1/1000 person-years for DPP4i initiators, 15.9/1000 person-years for GLP1-RA initiators versus 33.1/1000 person-years for SU initiators (aHR: DPP4i vs SU initiators = 0.64, 95%CI 0.52-0.80; GLP1RA vs SU initiators = 0.73, 95% CI 0.34-1.55).In this cohort of metformin monotherapy users, 2nd-line DPP4i use was associated with a 42% relative reduction in all-cause mortality and 36% reduction in MACE versus SUs, the most common 2nd-line therapy in our study. GLP-1RAs were not associated with adverse events in this cohort.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"