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Liraglutide probably the best second drug to prevent cardiovascular events in patients with T2DM who take metformin
Clinical Question
For patients with type 2 diabetes mellitus who take metformin, which additional drug is most effective at reducing microvascular and macrovascular cardiovascular events?
Bottom line
Although absolute event numbers are small and not always statistically significant, liraglutide is consistently the best second drug to prevent cardiovascular events in patients with type 2 diabetes mellitus who take metformin. The study that reported glycemic control favored sitagliptin, but liraglutide was significantly better at preventing cardiovascular events then sitagliptin. I'd rather live with a mediocre hemoglobin A1C level than die with a good one. A limitation is that there were no SGLT2 inhibitors in the study, because they were not FDA approved for use with metformin in 2013 when the study began. Clearly, a follow-up study comparing SGLT2 inhibitors with GLP-1 agonists as a second drug is needed. 1b
Reference
Study design: Randomized controlled trial (single-blinded)
Funding: Government
Setting: Outpatient (any)
Synopsis
These authors recruited 5047 participants with type 2 diabetes mellitus that had been present for less than 10 years and was diagnosed after the patient was 30 years of age. All participants were taking metformin. The authors included an active run-in period to try to titrate metformin to a target dose of 2000 mg per day; at the end of the run-in period, eligible participants had to have a hemoglobin A1C level between 6.8% and 8.5%. Those participants were randomly assigned 1 of 4 therapies: (1) insulin glargine at an initial dose of 20 U daily and adjusted upward, as needed; (2) the sulfonylurea glimepiride beginning at 1 mg to 2 mg to a maximum of 8 mg per day in divided doses; (3) liraglutide, a GLP-1 agonist, starting at 0.6 mg daily and titrating to 1.8 mg daily, as tolerated; or (4) the DPP-4 inhibitor sitagliptin 100 mg daily with the dose adjusted on the basis of renal function. At baseline, the participants' mean age was 57 years, 20% were Black, and most were being treated for comorbid hypertension and hyperlipidemia. After a mean of 5 years of follow-up, there was no significant difference among groups in microvascular outcomes like albuminuria, peripheral neuropathy, and renal impairment (defined as a GFR < 60 mL/min/1.73 m2). The primary cardiovascular outcome was the likelihood of any cardiovascular event, including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, unstable angina warranting hospitalization, hospitalization for heart failure, or any need for revascularization. This occurred significantly less often in the liraglutide group (6.6% vs 9.0% - 9.6% for the other groups; hazard ratio significantly lower for liraglutide vs sitagliptin comparison 0.68; 95% CI 0.51 - 0.90). Liraglutide also had the numerically lowest rate of major adverse cardiovascular events (3.8% vs 4.7% - 5.5%), hospitalizations for heart failure (1.1% vs 2.1% - 2.4%), cardiovascular death (0.7% vs 1.3% - 1.7%), and all-cause mortality (2.1% vs 3.2% - 3.4%).
Reviewer
Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA
Comments
Inhibiteur du GLP-1
Il est bon de savoir que le liraglutide a un bénéfice cardio-vasculaire. Et comme le réviseur mentionne une comparaison avec les inhibiteurs du SGLT-2 sera intéressant
Liraglutide to prevent cardiovascular events
Results seem clinically important. Re: no comparison with SGLT2 inhibitors - the study started in 2013 and took 9 years to publication. If one were to start a comparative study today with liraglutide vs SGLT2 inhibitors by the time it is published (with any luck in another 9 years) there will likely be another new class of drugs being used on diabetics. Bottom line is that we are pretty much doomed to be always 9 years behind in this area of knowledge. Yikes! Maybe we need to look for alternative clinically relevant outcomes that occur sooner and more frequently that what is used now so we can get answers sooner.
Liraglutide in T2DM
Good to know Liraglutide helps reduce cardiac events, even with only moderate glycemic control.
Think POEM Bottom Line has one line which seems misleading
The reference article has conclusion: In participants with type 2 diabetes, the incidences of microvascular complications and death were not materially different among the four treatment groups. The POEM bottom line includes "I'd rather live with a mediocre hemoglobin A1C level than die with a good one" which suggests less mortality which is not as per "conclusion" -- actual difference is cardiovascular events.
liraglutide and metformin
decrease cvs outcomes