My Type 2 Diabetes “Topic Alert” at Medscape recently emailed “Treating the Obese Diabetic,” an article published in Expert Reviews in Clinical Pharmacology at www.expert-reviews.com. It is a thorough, comprehensive and, in my opinion, balanced review of anti-diabetic pharmacological agents for the treatment of the obese type 2 diabetic. It also, as so many articles in the mainstream medical literature do these days, seems to me to make a big push to boost the business of the bariatric surgery industry. They’ve got boat payments to make and apparently are underemployed, as so many are today.
I can spare you having to read the whole paper. The abstract is brief and to the point. Here it is in its entirety:
“Type 2 diabetes and obesity are intimately linked; reduction of bodyweight improves glycemic control, mortality and morbidity. Treating obesity in the diabetic is hampered as some diabetic treatments lead to weight gain. Bariatric surgery is currently the most effective antiobesity treatment and causes long-term remission of diabetes in many patients. However, surgery has a high cost and is associated with a significant risk of complications, and in practical terms only limited numbers can undergo this therapy. The choice of pharmacological agents suitable for treatment of diabetes and obesity is currently limited. The glucagon-like peptide-1 receptor agonists improve glycemia and induce a modest weight loss, but there are doubts over their long-term safety. New drugs such as lorcaserin and phentermine/topiramate are being approved for obesity and have modest, salutary effects on glycemia, but again long-term safety is unclear. This article will also examine some future avenues for development, including gut hormone analogues that promise to combine powerful weight reduction with beneficial effects on glucose metabolism.”
The only pharmacological agent that gets a clean bill of health in this comprehensive review is metformin. All the others come with qualifiers like weight gain (!) and doubts over their long-term safety. Here is their review of metformin:
“Metformin, as per current American Diabetes Association (ADA) and European Association for the Study of Diabetes recommendations, is the first-line medication used for those with Type 2 diabetes and has an established safety record. It inhibits hepatic gluconeogenesis, and to a lesser extent glycogenolysis, but also increases insulin sensitivity. The UKPDS 34 study suggested improved cardiovascular (CV) outcomes in those taking metformin, although recent meta-analyses have failed to confirm this. Metformin not only offers useful glycemic control but has also been shown in some trials to induce weight loss, although two meta-analyses comparing metformin to placebo have shown its overall long-term effect appears to be weight neutral. Metformin has been in use clinically since the 1950s (in the USA since 1995), so it has a well-understood long-term safety profile with the most common side effects being transient gastrointestinal symptoms. Lactic acidosis is a rare side effect but cases have been reported in the literature.”
The Expert Commentary is succinct and pithy. The first paragraph tells the story. The rest of this section is also a good read.
“Faced with a newly diagnosed obese diabetic patient in a real world setting, it is important to ensure that the antidiabetic medications prescribed are effective and safe, without inducing weight gain. Ideally, our therapeutic strategy would utilize treatments with a long-term safety record that can induce weight loss and have been shown to improve CV outcomes. The only two treatments that offer this level of evidence at present are bariatric surgery and metformin.”
The paper includes 204 references and has a very interesting forward-looking “Five-year View” section near the end which is worth a look for any healthcare professionals among my readers. The “Sidebar” titled “Key Issues” summarizes the paper:
· Bariatric surgery is currently the most effective route to tackle the linked pathologies of diabetes and obesity. It produces durable weight loss and long-term remission of diabetes. In addition, cardiovascular morbidity and overall mortality are reduced in those diabetics who undergo surgery.
· Mechanistically, the improvement in glycemia following some forms of bariatric surgery, such as Roux-en-Y gastric bypass, may be driven by changes in gut hormone levels, thus providing a potentially attractive target for future medical therapies to treat diabesity.
· GLP-1 analogues produce significant weight loss along with an improvement in glycemia. DPP-IV inhibitors are well tolerated, effective and weight neutral. Neither therapy has a proven long-term safety record nor definitive evidence of benefit on cardiovascular risks.
· Recent additions to the US market are centrally acting lorcaserin and phentermine/topiramate. Both are effective at producing limited weight loss and have minor effects on glycemic control. Long-term safety data are lacking and they are still awaiting European approval.
Sadly, but understandably, this article treats only what the medical professional can do to “treat the obese diabetic:” write multiple scripts or, in eligible cases, recommend surgery. It does not address counseling the patient to change their diet to reduce the one thing that causes elevated glucose in the first place (in the disregulated metabolism): dietary carbohydrates.
If you read this blog regularly, you know the drill. In persons with insulin resistance, excess carbohydrates, and too much protein which can also be glucogenic (convert to glucose), cause elevated blood glucose. There is no “fix” for this condition once you have developed it except to eat many fewer carbs (and moderate amounts of protein). If you continue to eat a “balanced diet,” even with progressively more anti-diabetic medications, you will lose the battle. Your pancreas eventually will be unable to produce the extra insulin to transport your blood glucose to your cells that won’t take them up, and you will eventually become an insulin-dependent type 2 and/or develop the “inevitable complications” of “inadequately treated” type 2 diabetes: increased morbidity and mortality from a host of causes too tedious to mention.
So, you can let your doctor “treat the obese diabetic” in the manner prescribed in this paper, with the risks they frankly explain (and the outcomes I have suggested above), or… you can change your diet and “treat” yourself. It’s up to you.