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Glargine and liraglutide are the best second drugs after metformin for achieving tight glycemic control (in a study without SGLT2 inhibitors)
Clinical Question
For patients with fair glycemic control who are taking metformin, what is the best second drug to add to improve glycemic control?
Bottom line
If all you care about is glycemic outcomes, then liraglutide and insulin glargine are for you, although the latter has higher rates of serious adverse events. But we know that tight glycemic control in middle-aged and older patients with diabetes does not reduce, and may increase, mortality. What really matters is the impact on patient-oriented outcomes — and that is addressed in a companion POEM, Liraglutide probably the best second drug to prevent cardiovascular events in patients with T2DM who take metformin. 1b
Reference
Study design: Randomized controlled trial (single-blinded)
Funding: Government
Setting: Outpatient (any)
Synopsis
Finally. This study is long overdue. Glycemic outcomes are reported in this study and the more important cardiovascular outcomes are reported in a companion article in the same issue of the journal. The authors identified 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. A notable omission is SGLT2 inhibitors, now an important class of drugs but not approved by the FDA for use with metformin at the study start date of 2013. The 4 groups were similar at baseline, analysis was by intention to treat, and retention was more than 93% for the duration of the study. The mean age of participants was 57 years and 64% were men. After a 5-year mean duration of follow-up, retention was similar among groups. The primary glycemic outcome of having a hemoglobin A1C level greater than 7.0% occurred more often with sitagliptin (38%) and glimepiride (30%) than with liraglutide and insulin glargine (26%). However, serious adverse events were more common with glimepiride and insulin glargine, and severe hypoglycemia was more common with glimepiride (2.2%) than with the other medications (0.7% - 1.3%).
Reviewer
Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA
Comments
Glycemia Reduction in Type 2 Diabetes - Glycemic Outcomes
The conclusions of the reviewers are apparently different from the conclusions of the researchers.
Tight control of sugars not necessarily needed in middle age
Surprised that the risks and side effects of attempting tight glycemic control in the middle age and elderly is not really necessary
in my practice I did not notice that Sitagliptin is more eff
I am wondering since the study was conducted for few years why the study did not report cardiovascular outcomes, CHF , etc
also it did not since that DDP4 sitagliptin was more effective than Liraglutide in reducing HbaA1c I am concerned about adherence, randomization and blindness
Interesting
I find this relevant in my practice as Family Physician and Hospitalist. Potentially useful for Emergency Medicine as well.
liraglutide and glimepride in dm
2nd best after metformin