How Safe Are New Medications for Type 2 Diabetes?
June 15, 2019
By Joseph E. Scherger, MD, MPH
Core Faculty, Eisenhower Health Family Medicine Residency Program, Eisenhower Health Center, La Quinta, CA; Clinical Professor, Keck School of Medicine, University of Southern California, Los Angeles
Dr. Scherger reports no financial relationships relevant to this field of study.
SYNOPSIS: In recent years, new medications have been approved for the management of type 2 diabetes, generally after metformin is given. The FDA has reported 55 cases of Fournier’s gangrene in patients using SGLT2 inhibitors. These medications may not be worth the risk when lifestyle alternatives are available.
SOURCE: Bersoff-Matcha SJ, Chamberlain C, Cao C, et al. Fournier gangrene associated with sodium-glucose cotransporter-2 inhibitors: A review of spontaneous postmarketing cases. Ann Intern Med 2019; May 7. doi: 10.7326/M19-0085. [Epub ahead of print].
The FDA released a report of 55 cases of Fournier’s gangrene (FG) in patients who received SGLT2 inhibitors between March 1, 2013, and Jan. 31, 2019. The patients ranged in age from 33 to 87 years. Thirty-nine were men and 16 were women. The time for onset of this serious complication ranged from five days to 49 months. All the patients had surgical debridement and were severely ill. Other complications included sepsis or septic shock (nine patients), diabetic ketoacidosis (eight patients), and acute kidney injury (four patients). Eight patients underwent fecal diversion surgery, two patients developed necrotizing fasciitis of the lower extremity and required an amputation, and three patients died.
For comparison, the FDA identified 19 cases of FG with other antiglycemic medications during a longer period, from 1984 to Jan. 31, 2019. Eight of these patients were on metformin, six were on insulin glargine, two were on short-acting insulin, two were on sitagliptin plus metformin, and one was on dulaglutide. These patients ranged in age from 42 to 79 years. Two patients died.
At the time of this report, the FDA is calling for more awareness among physicians regarding this major complication for patients taking an SGLT2 inhibitor.
COMMENTARY
In recent years, many new medications have been approved to treat type 2 diabetes. These have been grouped into several classes based on their mechanism of action. All except metformin and the sulfonylureas are expensive. The FDA report is alarming in that FG is a major complication certain to harm patients, if not lead to their mortality.
Increasingly, healthcare professionals recognize that the major cause of type 2 diabetes is insulin resistance resulting from a diet high in processed carbohydrates.1 A growing number of clinics and academic health centers are reversing type 2 diabetes using a very low carbohydrate diet and intermittent fasting.1-3 In The Diabetes Code by Jason Fung, part four of the book is titled, “How Not to Treat Type 2 Diabetes.”1 Here, Fung details each medication and cites why they are counterproductive in managing the underlying disease.
While the medications may make the numbers look better, such as blood sugar and HbA1c, they generally make disease characteristics such as body weight, insulin resistance, and fatty liver disease worse, or do not reduce the complications of diabetes (e.g., heart disease). SGLT2 inhibitors are not the only medications for type 2 diabetes that can produce major side effects. Insulin causes hypoglycemia, increases weight gain, worsens metabolic syndrome, increases overall mortality, and increases the risk of cancer.4-6 Similar side effects occur with taking sulfonylureas.1 Thiazolidinediones fell out of use because of increased heart disease and cancer risk.7,8 Taking DPP-4 inhibitors does not lead to weight gain and can be effective against diabetes, but using these inhibitors does not lower heart disease risk.9
Since studying this new material on reversing type 2 diabetes through diet and other lifestyle measures such as daily exercise, I only treat this disease with diet and metformin, usually at the lower dose of 500 mg twice daily. I have seen patients lower their HbA1c from very high levels (over 12) to normal. Motivational counseling and lifestyle education are the key skills my team and I use to reverse this disease. Most patients are not aware that their diabetes is reversible. American medicine and medical education are centered on prescribing medications and performing procedures at great cost to society. My team manages chronic diseases that are reversible through lifestyle changes.
There is an exciting paradigm shift underway that all primary care physicians should be embracing. We can restore health in ways we never thought possible. Not all patients are willing to change, and we will still have to provide disease management (what I call palliative care) to some patients with type 2 diabetes and other reversible chronic health problems.
REFERENCES
- Fung J. The Diabetes Code: Prevent and Reverse Type 2 Diabetes Naturally. Vancouver: Greystone Books; 2018.
- HealClinics. Available at: http://bit.ly/2YRDxYQ. Accessed May 28, 2019.
- Hallberg S. Reversing type 2 diabetes starts with ignoring the guidelines. Available at: http://bit.ly/2Wt8chy. Accessed May 28, 2019.
- Geller AI, Shehab N, Lovegrove MC, et al. National estimates of insulin-related hypoglycemia and errors leading to emergency department visits and hospitalizations. JAMA Intern Med 2014;174:678-686.
- Currie CJ, Poole CD, Evans M, et al. Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapies in type 2 diabetes. J Clin Endocrinol Metab 2013;98:668-677.
- Bowker SL, Majumdar SR, Veugelers P, et al. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 2006;29:254-258.
- Nissen SE, Wolski K. Rosiglitazone revisited: An updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med 2010;170:1191-1201.
- Tuccori M, Filion KB, Yin H, et al. Pioglitazone use and risk of bladder cancer: Population based cohort study. BMJ 2016;30:352:i1541.
- Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015;373:232-242.
In recent years, new medications have been approved for the management of type 2 diabetes, generally after metformin is given. The FDA has reported 55 cases of Fournier’s gangrene in patients using SGLT2 inhibitors. These medications may not be worth the risk when lifestyle alternatives are available.
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