What’s new for diabetes management and prevention

January 6, 2016

From new ways of predicting who will and won’t develop diabetes, to new diabetes meds, to new evidence regarding which anti-vascular endothelial growth factor (VEGF) might be better for your specific patient, the last year has given us better tools for helping our patients with diabetes.

From new ways of predicting who will and won’t develop diabetes, to new diabetes meds, to new evidence regarding which anti-vascular endothelial growth factor (VEGF) might be better for your specific patient, the last year has given us better tools for helping our patients with diabetes.

A number of interesting developments have arisen in the last year concerning risk assessment, treatment, and management of both diabetes and diabetes-related eye disease. The stage has been set by the increasing prevalence of diabetes, with 29.1 million Americans having diabetes, and another 86 million having pre-diabetes.1 More recently, analysis published recently in JAMA shows that about 12 percent of U.S. adults have diabetes, with more than half of the adult population having either diabetes or pre-diabetes, including an astounding 83 percent of U.S. adults over the age of 65 years.2 Worldwide, diabetes rates continue to climb, particularly in Asia. In fact, if we total the number of people living with diabetes in China (100 million), India (50 million), and the U.S., this amalgam would represent the third most populous country in the world.3

Clearly, we need to do a better job of identifying those at highest risk for development of both diabetes and especially sight-threatening eye disease. The other thing we need is a whole lot of prevention.

More diabetes: Improve and protect your next patient with diabetes

Risk factors for type 2 diabetes

Some interesting and novel risk factors for type 2 diabetes (T2DM) have arisen within the last year, including alterations in the gut microbiome that fosters insulin resistance, at least some of which is attributable to both excess consumption of refined carbohydrates and non-nutritive sweeteners like aspartame and sucralose.3,4 Elevated liver enzymes ALT and AST also have been shown to be highly predictive of T2DM, particularly in women, and these are commonly associated with non-alcoholic fatty liver disease (NAFLD).5

Both of these findings bolster evidence that avoidance of added dietary sugars (the World Health Organization now recommends less than 40 grams per day, with an ideal target less than 25 grams per day)6 will lower diabetes risk at a population level. Lifestyle intervention continues to trump metformin for preventing T2DM over 15 years in high-risk subjects from the Diabetes Prevention Program (DPP), with 27 percent and 18 percent reduced incidence comparing 100 minutes/week walking to metformin vs. no intervention.7 Interestingly, a composite index of microvascular complications did not differ significantly between the treatment groups, though women assigned to the “lifestyle” group were about 22 percent less likely to experience any microvascular complication, including retinopathy.

Next: The latest diabetes medications

 

The latest diabetes medications

A number of new diabetes medications have become available, including two new glucagon-like peptide 1 (GLP-1) agonists: Trulicity, (dulaglutide, Lilly) and Tanzeum (albiglutide, GSK), which improve post-meal insulin production, reduce glucagon secretion, suppress appetite, and assist with weight loss-significant benefits for patients above ideal body weight (additionally, Novo received FDA approval for double-strength Victoza (liraglutide), trade name Saxenda for weight loss). A new sodium glucose transporter -2 (SGLT2) inhibitor was also released in the U.S., Jardiance (empagliflozin, Boehringer). These oral drugs lower blood sugar by reducing resorption of serum glucose in the proximal renal tubule, leading to urinary excretion of glucose, reduced blood pressure, and weight loss.

Medical Economics: Night-shift workers, poor sleepers at risk for diabetes

A major finding of the EMPA-REG study is that type 2 diabetes patients with high cardiovascular risk placed on empagliflozin were 38 percent less likely to die from cardiovascular causes compared to patients on other diabetes meds.8 Two other trials with SGLT2 inhibitors are ongoing to see if this cardiovascular (CV) protection is a class effect. If so, these drugs are anticipated to become major second-line agents after metformin for treatment of patients with T2DM.

Next: The latest in diabetic eye disease

 

The latest in diabetic eye disease

In regard to diabetic eye disease, the evidence grows that anti-VEGF drugs are superior to laser therapy for diabetic macular edema (DME). Three-year data with ranizibumab (Lucentis, Genentech) and 100-week data with aflibercept (Eylea, Regeneron) show that visual gains are maintained with these agents and are superior to gird or focal macular laser in isolation.9,10

The long-awaited Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol T results were released last May and showed that ranizibumab, aflibercept, and bevacizumab (Avastin, Genentech) were roughly comparable in efficacy for treatment of center-involved DME.12 Subgroup analysis did show, however, that patients with baseline visual acuities of 20/50 or worse achieved better visual outcomes with aflibercept compared with the other two agents (about one additional line of acuity. Adverse events were slightly elevated but infrequent and about the same in all three groups-it must be remembered that patients with diabetic retinopathy (DR) and/or DME have higher CV risk to begin with. Both Lucentis and Eylea were also granted additional FDA indications for treating non-proliferative DR in patients with co-existing DME; of course, both remain far more costly than their off-label counterpart, Avastin.

I had the pleasure of attending a special ARVO Diabetic Retinopathy Small Meeting at U.S. National Institutes of Health at the end of August 2015. Attendees heard from a number of esteemed investigators and clinicians about groundbreaking work into the pathophysiology, genetics, and treatment of DR and DME. I look forward to sharing with you a few items that particularly piqued my interest in my next column.

More from Dr. Chous: The importance of multidisciplinary care for diabetes

 

References

1. CDC National Diabetes Statistics Report 2014. Available at: http://www.cdc.gov/diabetes/data/statistics/2014statisticsreport.html. accessed 12/08/2015.

2. Menke A, Casagrande S, Geiss L, et al. Prevalence of and Trends in Diabetes Among Adults in the United States, 1988-2012. JAMA. 2015 Sep 8;314(10):1021-9.

3. Guariguata L, Whiting DR, Hmableton I, et al. Global estimates for diabetes prevalence in 2013 and projections for 2035. Diabetes Res Clin Pract. 2014 Feb;103(2):137-49.

4. Barlow GM, Yu A, Mathur R. Role of the Gut Microbiome in Obesity and Diabetes Mellitus. Nutr Clin Pract. 2015 Dec;30(6):787-97.  

5. Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct 9;514(7521):181-6.

6. Ko SH, Baeg MK, Han KD, et al. Increased liver markers are associated with higher risk of type 2 diabetes. World J Gastroenterol. 2015 Jun 28;21(24):7478-87.

7. World Health Organization. WHO calls on countries to reduce sugars intake among adults and children. Available at:  http://www.who.int/mediacentre/news/releases/2015/sugar-guideline/en/. Accessed: 9/10/2015.

8. Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015 Nov;3(11):866-75.  

9. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28.

10. Boyer DS, Nguyen QD, Brown DM, et al. Outcomes with As-Needed Ranibizumab after Initial Monthly Therapy: Long-Term Outcomes of the Phase III RIDE and RISE Trials. Ophthalmology. 2015 Dec;122(12):2504-2513.

11. Brown DM, Schmidt-Erfurth U, Do DV, et al. Intravitreal Aflibercept for Diabetic Macular Edema: 100-Week Results From the VISTA and VIVID Studies. Ophthalmology. 2015 Oct;122(10):2044-52.

12. Diabetic Retinopathy Clinical Research Network, Wells JA, Glassman AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015 Mar 26;372(13):1193-203.