All FDA-approved diabetes medications have proven to be effective in lowering A1C. And several major studies have shown that a lower A1C is associated with a lower risk of complications, especially complications affecting the kidneys (nephropathy), eyes (retinopathy), and nerves (neuropathy).
Lower A1C also lowers risk of heart attacks and strokes. But do these findings imply better outcomes in terms of longevity? And are some drugs better than others?
Results from the American Diabetes Association's Annual Scientific Sessions
A few years ago, a large study showed that use of sulfonylureas (e.g. glipizide, glyburide, glimeperide) was associated with a 24-60% higher risk of death than use of metformin (1).
The same study showed that pioglitazone had a 30-39% lower risk of death than metformin, and found that rosiglitazone had a higher risk of death than pioglitazone.
This was followed by a controversy over whether one particular type of medication had a higher risk than other medications.
In response, the FDA demanded that all new diabetes medications undergo large, long term, cardiovascular outcome trials (CVOT) to verify that they are not associated with increased risk of heart attack, heart failure or stroke.
At the American Diabetes Association (ADA) meeting held in 2016, the results of two of these CVOT studies were reported.
The LEADER trial evaluated the safety of liraglutide in people with type 2 diabetes who were at high risk for cardiovascular disease. Based on 4½ years of follow-up of more than 8,000 patients with type 2 diabetes, the study found a significant (15%) reduction in death from any cause and a 12% reduction in death from any cardiovascular cause.
The differences became apparent after about 1½ years of treatment (2). More studies are currently underway to determine whether this finding applies to other similar drugs as well, or whether it is specific to liraglutide.
At the same ADA meeting, another study reported on the safety of another medication, empagliflozin.
Empagliflozin is a member of the SGLT-2 class of drugs. A previous report of this study was presented at the European Association for the Study of Diabetes (EASD) the same year.
Empagliflozin is associated with a dramatic 32-38% reduction in death and rates of hospitalization for heart failure (3). Now, the EMPA-REG OUTCOME study has reported that empagliflozin is associated with a dramatic (39 to 55%) reduction in risk of development or progression of kidney disease in people with type 2 diabetes (4).
This benefit begins almost immediately after starting the medication. Similar studies are underway to evaluate cardiovascular safety of two other medications in the same class (SGLT-2 inhibitors).
Results will be available within the next few years.
These new and dramatic results from the LEADER study (2) and the EMPA-REG OUTCOME study (3,4) reported at the ADA are extremely promising and provide tremendous encouragement that complications of diabetes can be prevented while adding many years to a happy, healthy life.
- Tzoulaki I. et al. BMJ 2009;339:b4731 <doi:10.1136/bmj.b4731>. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database
- Mars SP, for the LEADER Steering Committee on behalf of the LEADER Trial Investigators. New England Journal of Medicine. June 13, 2016. <DOI: 10.1056/NEJMoa1603827>. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
- Zinman B, et al. for the EMPA-REG OUTCOME Investigators. New England Journal of Medicine. 2015; 373:2117-2128. November 26, 2015 <DOI: 10.1056/NEJMoa1504720> . EMPA-REG Outcome. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. See also: http://www.ndei.org/conference-coverage-empa-reg-outcome-trial-empagliflozin-reduces-cardiovascular-deaths-SGLT2-inhibitor-EASD-congress-2015.aspx
- Wanner C et al. and the EMPA-REG OUTCOME Investigators. N Engl J Med. 2016 Jun 14. [Epub ahead of print] PMID: 27299675. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. http://www.nejm.org/doi/full/10.1056/NEJMoa1515920
This guest post was written by David Rodbard, M.D. Dr. Rodbard is an endocrinologist whose had a long career as a clinician and scientist working in mathematics, statistics, modeling, and computing at NIH. He started developing computer programs for analyzing glucose data in the mid-1980’s, and he’s worked with multiple companies developing glucose meters and CGM sensors. He has developed a dozen new methods to display glucose and insulin data. Currently, he is working on ‘artificial intelligence’ to permit computers to interpret glucose, insulin, medication, food, intake, and activity data—the exact kinds of data collected and used by One Drop.
Dr. Rodbard is also married to an endocrinologist Dr. Rodbard (2) with a large active private practice largely devoted to diabetes—both T1 and T2. She does extensive clinical trials of new medications and new types of insulin, and has also developed algorithms to help physicians select therapy for people with diabetes.