Category Archives: Drugs for Diabetes

Do Certain Diabetes Drugs Protect the Heart and Kidneys?

 

Blood pressure control is also extremely important for protection of heart and kidneys

I’ve been reticent to tout the putative heart-protective effects of diabetes drugs in the classes called SGLT2 inhibitors and GLP-1 receptor agonists. Frankly, their supposed kidney-protective effects haven’t even been on my radar. My hesitation to report on these matters stems from:

Maybe if Big Pharma sent me a nice check….

The GLP-1 receptor agonists seem to have beneficial effects on both heart and kidney. With SGLT2 inhibitors, renal benefits may be more prominent than cardiac. Also note that any beneficial heart or renal effects may be attributable only to certain drug within the class, and not a class effect.

For what it’s worth, the American Diabetes Association recently hosted a conference on these issues. I assume the ADA endorses the report written by three experts, two of whom have received some sort of compensation from pharmaceutical companies. This doesn’t necessarily mean they are biased. Some excerpts:

Since patients with diabetes are at increased risk for CV [cardiovascular] and renal events, reducing the risk of these events is of primary interest to improve outcomes in the long-term. [Cardiovascular events usually refers to heart attacks, strokes, and death from those. Renal events would be high loss of protein through the kidneys, impaired kidney function or chronic kidney disease, or the need for dialysis.]

SGLT2 inhibitors and GLP-1 RAs have dramatically changed the treatment landscape of type 2 diabetes due to their established CV benefits, and the observed improvements in renal function seen with these classes of agents are currently undergoing intense investigation.

***

It is now apparent that both SGLT2 inhibitors and GLP-1 RAs show consistent reductions in major adverse cardiovascular events for patients with established cardiovascular (CV) disease, and both appear to have renal benefits as well.

***

The nephron is the microscopic structural and functional unit of the kidney.

Renal effects of GLP-1 receptor agonists

These drugs may exert their beneficial actions on the kidneys through their effects on lowering blood glucose and blood pressure and by reducing the levels of insulin.

For GLP-1RAs, these [studies] include ELIXA with lixisenatide, LEADER with liraglutide, SUSTAIN-6 with semaglutide, EXCSEL with exenatide once-weekly, HARMONY with albiglutide, and REWIND with dulaglutide.

All these studies indicate that albuminuria [protein loss through urine] is reduced during treatment with GLP-1 RAs, and eGFR [estimated glomerular filtration rate, a measure of kidney function] appears to be stabilized.

These benefits are seen independently of HbA1c, weight, and blood pressure variations.

***

Heart attack is only one type of cardiovascular event

Cardiovascular effects of GLP-1 receptor agonists

Large CV outcomes trials with GLP-1 RAs have shown that these agents can reduce the risk of major adverse CV events, CV mortality, and all-cause mortality.

These CV benefits appear to be related to four distinct mechanisms:

    • Improve myocardial [heart muscle] performance in ischemic heart failure [caused by poor blood flow to heart]
    • Improve myocardial survival in ischemic heart disease
    • Ameliorate endothelial dysfunction [endothelium is the lining of arteries]
    • Decrease markers of CV risk.

***

Renal effects of SGLT2 inhibitors

  • However, many potential mechanisms have been linked to the renoprotective effects of SGLT2 inhibitors.
  • These include reduction of blood pressure, improved metabolic parameters, reduced volume overload, reduction in albuminuria, and glomerular pressure.
  • For the latter, SGLT2 inhibition appears to reduce hyperfiltration via a tubuloglomerular feedback mechanism.
  • Clinical data from CV outcomes trials have shown consistent variations in eGFR and reduction in death from renal causes with empagliflozin, canagliflozin, and dapagliflozin.
  • However, to gain more information about the renal effects of these agents, dedicated renal outcomes trials are needed to study reductions in albuminuria, changes in eGFR, number of patients reaching end-stage renal disease, need for dialysis, and deaths due to kidney failure.

***

Key Messages from the authors

Large CV outcomes trials have shown that both SGLT2 inhibitors and GLP-1 RAs are associated with significant reductions in CV events in patients with elevated CV risk.

From CV outcomes trials both classes of agents also appear to have renal benefits, although large dedicated studies are needed to establish the magnitude of this potential benefit

The mechanism of action at the basis of CV and renal benefits of SGLT2 inhibitors and GLP-1 RAs is complex, multifactorial, and still not completely understood.

 

I’m still skeptical but will keep an open mind.

Steve Parker, M.D.

PS: Bold emphasis above is mine.

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Filed under coronary heart disease, Drugs for Diabetes, Heart Disease, kidney disease, Stroke

Mediterranean Diet Reduces Need For Diabetes Medications

diabetic mediterranean diet, Steve Parker MD

Pharmacist counting pills

From Diabetes Care:

OBJECTIVE

To examine the effects of two Mediterranean eating plans (Med-EatPlans) versus a low-fat eating plan on the need for glucose-lowering medications.

RESEARCH DESIGN AND METHODS

From the Prevención con Dieta Mediterránea (PREDIMED) trial, we selected 3,230 participants with type 2 diabetes at baseline. These participants were randomly assigned to one of three eating plans: Med-EatPlan supplemented with extra-virgin olive oil (EVOO), Med-EatPlan supplemented with mixed nuts, or a low-fat eating plan (control). In a subgroup (15%), the allocation was done in small clusters instead of using individual randomization, and the clustering effect was taken into account in the statistical analysis. In multivariable time-to-event survival models, we assessed two outcomes: 1) introduction of the first glucose-lowering medication (oral or injectable) among participants on lifestyle management at enrollment and 2) insulin initiation.

RESULTS

After a median follow-up of 3.2 years, in multivariable analyses adjusting for baseline characteristics and propensity scores, the hazard ratios (HRs) of starting a first glucose-lowering medication were 0.78 (95% CI 0.62–0.98) for Med-EatPlan + EVOO and 0.89 (0.71–1.12) for Med-EatPlan + nuts, compared with the control eating plan. After a median follow-up of 5.1 years, the adjusted HRs of starting insulin treatment were 0.87 (0.68–1.11) for Med-EatPlan + EVOO and 0.89 (0.69–1.14) for Med-EatPlan + nuts compared with the control eating plan.

CONCLUSIONS

Among participants with type 2 diabetes, a Med-EatPlan + EVOO may delay the introduction of new-onset glucose-lowering medications. The Med-EatPlan did not result in a significantly lower need for insulin.

Source: Effects of a Mediterranean Eating Plan on the Need for Glucose-Lowering Medications in Participants With Type 2 Diabetes: A Subgroup Analysis of the PREDIMED Trial | Diabetes Care

Steve Parker, M.D.

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Filed under Drugs for Diabetes, Health Benefits, Mediterranean Diet

Is Cinnamon a Legitimate Treatment for Diabetes?

What type of cinnamon is this?

Be aware that there are several types of cinnamon.

Pharmacist Scott Gavura writes at Science Based Medicine:

Given the consequences of diabetes, self-management is something I want to encourage, not discourage. Without a commitment from the patient to take an active role in managing their diabetes, any treatment plan is doomed to fail. So is self-treatment with dietary supplements a wise idea? There’s an array available, and patients regularly ask about the latest treatment “Big Pharma doesn’t want you to know about”. That treatment used to be chromium. Ginseng was popular for a time, too. Fenugreek and bitter melon are used as well. One of the most persistently popular treatments is cinnamon. Like any other herbal remedy, most sources will tell you that it’s been used for “thousands of years” as a medicinal herb. As a treatment for diabetes, I have my doubts. While reports of diabetes go back to 1552 BCE, the ability to measure the effectiveness of any diabetes treatment only goes back a few decades. Interest in cinnamon as a treatment seems to have started with in vitro tests but gained some plausibility in 2003, when a study from Alam Khan suggested several grams of cassia cinnamon per day could lower fasting blood glucose. Khan randomized Type 2 diabetes to 1g, 3g, or 6g of cinnamon for 40 days. All three groups improved their fasting blood glucose, and blood lipid levels, but there was no effect on A1C.Like trials with any other supplement or herbal product, the primary question we must answer is “What exactly was studied?” The cinnamon you have in your kitchen may be a single species of plant or a mix of different cultivars. Ceylon cinnamon (Cinnamommum verum) is more commonly found in the West. Cassia cinnamon (Cinnamomum aromaticum) is the version of cinnamon that’s been studied in trials. The chemical hydroxychalcone has been identified as a potential active ingredient, which is believed to modify the sensitivity of cells to insulin, enhancing their uptake. If that’s the true mechanism of action, then it would work in a manner similar to that of the drugs Avandia, Actos, and metformin (Glucophage). Given the active ingredient (or ingredients) have not yet been definitively isolated, the issue of studying cinnamon is problematic. There’s no way to assess the potency of any batch, which complicates any evaluation. And that may be a reason why the research with cinnamon is inconsistent, and on balance, not impressive.

While the Khan study looked promising, supplementary studies have failed to consistently show beneficial effects.

Source: How effectively does cinnamon treat diabetes? – Science-Based Medicine

Steve Parker, M.D.

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Filed under Drugs for Diabetes, Supplements

Cross the Border for Affordable Insulin

Great article by Robin Cressman. Read the whole thing.

“Just a week before the trip [to Tijuana, Mexico], I was down to my very last vial of Humalog. It was June and I was close, but still so far, from hitting my $5,000 deductible for the year, which meant I was still paying full price out of pocket for all of my medical costs until I hit that figure. I had started the year low on supplies (a rookie mistake that I now know to avoid) and had been juggling bills from Dexcom, my doctor’s office, and my pump supplier for months, trying to only use our health savings account but often having to pull out credit cards to cover the costs. I called my pharmacy and asked to fill a single vial of Humalog, and the cost was $248.13. I hung up the phone. Instead I went to Walmart and for the first time bought vials of Novolin NPH and Regular for $24.99 each. It was those vials that were serving as my backup insulin a week later when I found myself in that pharmacy in Tijuana.”

Source: Crossing Borders to Afford Insulin – T1International

Whether it’s legal or not, I don’t know.

Steve Parker, M.D.

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Filed under Drugs for Diabetes, Uncategorized

FDA warns doctors  about rare occurrences of a serious infection of the genital area with SGLT2 inhibitor drugs

The infection is called Fournier Gangrene. It’s a nasty infection that I’ve seen only a few times, always in men. The FDA reports cases in both men and women taking SGLT2 inhibitors to treat their diabetes.

“Patients should seek medical attention immediately if you experience any symptoms of tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever above 100.4 F or a general feeling of being unwell. These symptoms can worsen quickly, so it is important to seek treatment right away.”

Source: FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes | FDA

Steve Parker, M.D.

PS: With the right diet, you’ll need fewer drugs to control your diabetes. So, fewer drug side effects and less expense.

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Filed under Diabetes Complications, Drugs for Diabetes

Do Nutritional Supplements Help Control Diabetes?

From Diabetes Care

“The routine use of chromium or vitamin D micronutrient supplements or any herbal supplements, including cinnamon, curcumin, or aloe vera, for improving glycemia in people with diabetes is not supported by evidence and is therefore not recommended.”

Source: Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report | Diabetes Care

Did Big Pharma pay for this article in Diabetes Care?

Steve Parker, M.D.

PS: The Low-Carb Mediterranean Diet typically reduces or eliminates the need for drugs or supplements to control diabetes.

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From 2003: Oral Magnesium Supplementation Improves Insulin Sensitivity and Metabolic Control in Type 2 Diabetes

Not the magnesium used in the study at hand

The study was done in northern Mexico and all participants were taking glibenclamide, a sulfonylurea known as glyburide in the U.S. Importantly, study participants had low blood magnesium levels at the outset.

So if you’re not a hypomagnesemic Mexican taking glibenclamide, results may not apply to you.

Nevertheless, results were impressive. Compared to the control group, magnesium supplementation…

  • reduced insulin resistance
  • fasting glucose was 144 mg/dl (185 in controls)
  • Hemoglobin A1c was 8% (10% in controls)

The experiment lasted 16 weeks and the specific form of magnesium used was magnesium chloride solution.

Maybe we should be checking magnesium levels more often. BTW, magnesium supplements are difficult for our bodies to absorb. I know of at least three magnesium compounds: oxide, citrate, and chloride. There are probably others. Degree of absorption varies from one to the other. Adding a supplement on top of kidney impairment could cause toxicity.

The researchers conclude:

Oral supplementation with MgCl2 solution restores serum magnesium levels, improving insulin sensitivity and metabolic control in type 2 diabetic patients with decreased serum magnesium levels.

Source: Oral Magnesium Supplementation Improves Insulin Sensitivity and Metabolic Control in Type 2 Diabetic Subjects | Diabetes Care

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