Stopping Prediabetes in Its Tracks: Simple Interventions that Work

Stopping Prediabetes in Its Tracks: Simple Interventions that Work

By Gary Pepper, M.D. and Sam Jeans MSc

In our previous article The Prediabetes Puzzle: What the Blood Tests Mean, we investigated controversies surrounding diabetes diagnosis.

There’s a clear lack of consensus surrounding thresholds for diagnosis of prediabetes, the tests used to measure blood sugar, and the way forward for those at risk of transitioning from prediabetes to diabetes.

If left untreated, at least 37% of individuals with prediabetes typically develop type 2 diabetes in 4 years. But, with appropriate and early intervention, this can be dramatically reduced to 17% or less.

Here, we’ll investigate what diabetes interventions are effective, including lifestyle changes and medication.

Early Interventions For Prediabetes

Diagnosis of prediabetes is a useful wake-up call for many.

A sedentary lifestyle, a poor diet…these are significant contributors to prediabetes, and fighting back to take back control of one’s health vastly decreases the likelihood of transitioning to diabetes. The earlier prediabetes is caught, the easier it is to tackle.

When prediabetes is diagnosed, people face a series of choices. Should you tackle it with lifestyle changes alone?

Will you stick to the plan for long enough to see the benefits?

Or is early intervention with medication a good idea? And if so, what medication?

The Impact of Diet And Exercise

Unsurprisingly, a healthy diet and exercise are essential for weight management and glycemic control. Sustained lifestyle improvements improve insulin sensitivity, decreasing blood sugar levels and stunting the development of full-blown diabetes.

But how effective are lifestyle interventions?

An influential study of lifestyle interventions, The Diabetes Prevention Program (DPP), demonstrated that a low-fat, low-calorie diet reduced the incidence of diabetes by 58% in individuals with prediabetes.

The study recommended a daily intake of less than 25% of total calories from fat, increased fiber intake, and reduced daily calorie intake to achieve 7% weight loss. It’s worth highlighting that the study involved 1,079 participants and was highly structured with a relatively strict regime of 16 taught sessions. Non-adherent participants were introduced to a “toolbox” of extra interventions.

Another major systematic review found that, after one and three years of lifestyle intervention, the risk of diabetes decreased by 36% to 54% compared to treatment as usual.

Several studies also found a reduced incidence of cardiovascular and microvascular illnesses (e.g., neuropathies). Even when blood sugar levels don’t drop to normal, lifestyle changes were shown to improve overall health and lower the risk of mortality.

Further, multiple studies show that lifestyle exercises are considerably more effective than medication alone:

“Lifestyle intervention decreased the incidence of type 2 diabetes by 58% compared with 31% in the metformin-treated group” The Diabetes Prevention Program (DPP).

In short, it’s certain that lifestyle changes can change the course of diabetes.

However, not everyone has access to targeted diabetes interventions like that provided by the DPP.

Self-led and clinician-supported lifestyle interventions are still effective – here’s what people can do.

What To Do

(Reminder: Any recommendations made here are for educational purposes only. Only your health care provider can prescribe lifestyle modifications or medications appropriate for you as an individual)

Firstly, it’s time to get moving. The American Diabetes Association (ADA) recommends at least 150 minutes of moderate-intensity aerobic exercise per week, with no more than two consecutive days without activity. Resistance training is also recommended at least twice a week if possible.,

In terms of diet, all the usual recommendations apply. Decrease saturated fat, sugar, refined carbs, and calories and swap for protein, fiber, and wholegrains.

Add plenty of fruit, veg, grains, legumes, nuts, and good fats like olive oils. Ditch processed food.

While any lower-fat, lower-calorie diet with plenty of fruit and veg is better than a heavily processed diet, the Mediterranean diet is shown to be particularly effective.

Characterized by high consumption of fruits, vegetables, whole grains, legumes, nuts, and olive oil, the Mediterranean diet performs better than other diets.

5-Step Plan for Reducing Diabetes Risk

Here is a 5-step plan to reduce the risk of diabetes through lifestyle changes:

  • 1. Weight management: Achieving and maintaining a healthy weight is crucial for diabetes prevention. The Diabetes Prevention Program (DPP) found that a modest weight loss of 5-7% of initial body weight significantly reduced the risk of developing type 2 diabetes in individuals with prediabetes. 5 to 7% is achievable for most people.
  • 2. Dietary modifications: Consuming a balanced and healthy diet is essential for diabetes prevention. The DPP recommended a low-fat, low-calorie diet with high consumption of fruits, vegetables, whole grains, legumes, and nuts.
  • 3. Physical activity: Regular exercise helps improve insulin sensitivity and aids in weight management. The American Diabetes Association (ADA) recommends at least 150 minutes of moderate-intensity aerobic exercise per week, with no more than two consecutive days without activity.
  • 4. Quit smoking: Smoking has been associated with an increased risk of developing type 2 diabetes. Quitting smoking can help reduce the risk of diabetes and various other health issues, including cardiovascular diseases and respiratory illnesses.
  • 5. Stress management: Chronic stress has been linked to an increased risk of developing type 2 diabetes. Adopting stress reduction techniques, such as mindfulness meditation, yoga, or engaging in hobbies and relaxation activities, can help manage stress and contribute to overall well-being, potentially reducing the risk of diabetes.

The positive effects of lifestyle changes start quite quickly – within days to weeks.

But, blood sugar levels can take months to years to come down. So, regular check-ups are essential, and don’t become disheartened if the impact isn’t immediate.

Diabetes Medication

Medications remain extremely important in treating diabetes.

Not everyone can commit to the lifestyle changes required to reduce blood sugar levels naturally.

For example, some with prediabetes may be unable to partake in intense exercise due to musculoskeletal issues, disabilities and complications from other diseases. But, of course, that isn’t to say that diet and healthy eating alone won’t have an impact.

The critical issue is, lifestyle interventions often aren’t adhered to for long enough to have an impact. Or in other words, people give up.

Studies place adherence to lifestyle interventions at around 50 to 60%. So over half of people give up in many cases. Those that give up are very likely to develop diabetes without other interventions.

This has led many health authorities to encourage medication almost immediately.

Diabetes Drugs are Changing

Diabetes medications remained fairly consistent for almost 50 years.

Metformin and thiazolidinediones (formerly known by the brand name Actos), in particular, have been considered highly reliable in treating diabetes.

There’s been an explosion in new diabetes drugs in recent years, with the 50-year-old metformin, although remaining the first choice, this dominance has been challenged in the last few years.

Newer peptide-1 (GLP-1) agonists (e.g., semaglutide/liraglutide with brand names like Victoza and Ozempic) and SGLT-2 inhibitors such as Jardiance and Invokana have grown in interest for their ability to lower blood sugar levels and reduce weight. While their performance for reducing blood sugar are very similar to older drugs, they may have a better combined impact on blood glucose and weight loss.

There’s an all-too-familiar issue at play, though. Liraglutide and semaglutide drugs are expensive.

An article published in the Wall Street Journal sums this up well, “The newer drugs cost more than metformin, however, and some patients might not be able to afford the out-of-pocket costs and need to go with metformin. Ozempic, for example, lists for nearly $900 a month, and Jardiance comes in at about $590 a month.”

So, what does this all mean for metformin and other diabetes drugs? Will they merely fade into the background?

Metformin: Still a Wonder Drug?

Metformin is still the world’s most widely used medication for treating type 2 diabetes and has demonstrated efficacy in preventing the progression from prediabetes to diabetes.

Metformin primarily reduces glucose production by the liver and increases insulin sensitivity in peripheral tissue.

The DPP revealed a 31% reduction in the incidence of diabetes in individuals with prediabetes treated with metformin compared to the control group. While combined metformin and lifestyle change was significantly more effective at 58%, metformin’s impact is still impressive.

The drug is generally well tolerated, with gastrointestinal side effects being the most common adverse events. Some patients do experience lower exercise tolerance after taking metformin, which may impede exercise interventions, but evidence suggests this is minimal in most cases. Metformin has been around for a long time, and there’s not much we don’t know about it – no nasty surprises means a lot. Furthermore, metformin costs pennies per month making the overall appeal of this drug for diabetes management almost unchallengeable.

However, despite its excellent safety and tolerability profile, we can see early indications that pharma is falling out of love with the drug.

Some 80% of those with diabetes are eligible for new drugs, according to this publication by WebMD. The report emphasizes Ozempic, which currently costs $814 to $1040 per month.

Indeed, higher profit margins on new drugs are hardly discouraging pharma from thrusting semaglutide/liraglutide into the limelight.

Another Contender: Pioglitazone

Another veteran diabetes drug, pioglitazone, originally marketed as Actos, has also demonstrated efficacy in preventing the progression from prediabetes to diabetes.

It works by increasing insulin sensitivity in peripheral tissues and reducing hepatic glucose production.

The ACT NOW study showed that pioglitazone reduced the risk of developing diabetes by 72% in individuals with impaired glucose tolerance – better than metformin and newer semaglutide/liraglutide drugs.

However, concerns that pioglitazone raised the risk of heart failure and carried a small risk of bladder cancer impacted its reputation in the early-2000s.

Pioglitazone: Dangerous or Disregarded?

A few studies have drawn attention to pioglitazone’s controversial status in diabetes treatment.

● One such 2014 article Pioglitazone: An Antidiabetic Drug with Cardiovascular Therapeutic Effects, concluded that pioglitazone has beneficial effects, contrary to some earlier concerns about its safety. In addition, they draw attention to the 2005 PROactive study, which demonstrated that pioglitazone reduced non-fatal myocardial infarction and stroke in patients with type 2 diabetes.

● Studies in 2007 and 2013 both encouraged new insights into the drug, the latter, published in the journal Diabetes Care, suggesting “more commonly used regimens (other than pioglitazone) are both less effective and more likely to result in worse safety outcomes.” The authors also address the concern of an increased risk of bladder cancer associated with pioglitazone use, stating that the evidence is inconclusive and the absolute risk, if any, is low.

● In 2021, another study Rethinking pioglitazone as a cardioprotective agent: a new perspective on an overlooked drug , further highlighted pioglitazone’s cardiovascular benefits, such as reducing the risk of major adverse cardiovascular events in certain patient populations.

As the pharmaceutical industry slowly shifts the emphasis to newer, more expensive peptide-1 (GLP-1) agonists and SGLT-2 blockers, it’s essential to remain mindful of longstanding, reliable drugs with well-understood safety profiles.

Pioglitazone and metformin are exceptionally well known to medical science. Although some practitioners imply that these older medications have become outdated, their long record of safety and efficacy should be a major plus when considering treatment options.

Summary: Preventing the Progression from Prediabetes to Type 2 Diabetes

Preventing the progression from prediabetes to diabetes is critical. This important window of intervention shouldn’t be ignored.

Evidence-based strategies, including weight management through diet and exercise and the use of medications such as metformin, pioglitazone, and newer agents such as Ozempic , can significantly reduce the risk of developing diabetes in individuals with prediabetes.

Lifestyle changes are extremely effective and can have a transformative effect. People must stick to them – don’t be part of the 50%+ of those who give up.

When it comes to medication, old is still sometimes gold. Newer medications may grab the headlines (and advertising time), the reliability and affordability of older medications like metformin should not be overlooked

Disclaimer; This publication/article, as well as all publications originating at www.metabolism.com,  is/are for the sole purpose of information and education and not intended as medical treatment or advice or in anyway to substitute for the care rendered by a personal healthcare provider. We acknowledge that in the rapidly evolving field of medical science and treatment, our publication may contain unintentional informational gaps and inaccuracies. If so, we appreciate feedback on these deficiencies so we may correct them. Only your personal health care provider can supply treatment and advice suitable for your needs. Users of www.metabolism.com understand that their use of the website is governed by the disclaimer and terms of use found at www.metabolism.com.

New Diabetes Medications Cost 100 Times More than Established Treatments

by Gary Pepper, M.D.

“New is not always better.” This caution seems reasonable when considering the value of the recently approved medications for treatment of Type 2 (adult type) diabetes.  These drugs include three new classes of medication referred to as GLP-1 analogs, DPP-4 inhibitors and most recently SGLT-2 inhibitors. The focus of this discussion will be the most widely prescribed of the newcomers, the DPP-4 inhibitors.

The first thing consumers will notice about thehttp://www.dreamstime.com/stock-photo-expensive-medicine-image3053770 new diabetes medications are their TV commercial friendly names,  Januvia, Onglyza, Tradjenta, and Nesina.  Mix these newcomer drugs together into a single pill with the venerable low cost generic metformin and the names becomes Janumet, Kombiglyze, Jentadueto, and Kazano.

The next thing a consumer will notice is the price tag. At the local pharmacy in Jupiter, Florida the retail prices of a 3 month supply of Januvia, Onglyza or Tradjenta are all about $1100.  A three month supply of the established generic drug, glipizide, is $9.99 and metformin is between zero and $41. (more…)

Infertility to Acne: Treatment and Prevention of Polycystic Ovarian Syndrome. Part 2

Worried about pregnancyIn part one of this series we looked at the cause of polycystic ovarian syndrome (PCOS) and the many complications it causes. Weight gain, acne, excess hair growth on the face and body,  high cholesterol and high blood sugar due to insulin resistance are among the problems associated with PCOS.  One particular area of concern for PCOS sufferers is infertility due to lack of ovulation. PCOS is the cause of anovulatory infertility in  3 out of 4 cases. Before the acceptance of medical therapy for infertility due to PCOS  a surgical approach referred to as a wedge resection of the ovary was performed which allowed patients with PCOS to ovulate and conceive normally. Low success rates with this procedure, complications of surgery and improved medical therapies have all resulted in the end of this type of treatment in most situations.  At present, treatment of infertility associated with PCOS generally consists of using a drug to combat insulin resistance known as metformin often in combination with the fertility drug clomid, which has a high rate of success.

Treatment of the excess hair growth associated with PCOS often consists of using the drug spironalactone and the use of birth control pills. Spironalactone is a very interesting drug used for decades as a salt depleting diuretic but also has an effect to block the action of the male hormone testosterone. The action of spironalactone to block testosterone was discovered when it was noticed that men using this diuretic developed tender nipples and breast enlargement (gynecomastia). Oral contraceptive agents are also useful to combat hirsutism because these agents also cause reduce testosterone levels by putting the ovary in a dormant “resting” state.  Cosmetic procedures are always another option to treat unwanted hair growth. Laser hair removal appears to be replacing the older modality of electrolysis for this purpose.

Can PCOS be cured? Once PCOS develops it can be controlled but not cured unless the ovaries are removed. At menopause  PCOS-related problems diminish as the ovary stops making sex hormones including testosterone which is one of the culprits during the reproductive years. A recent study published this year in the journal Pediatric Endocrinology showed that using metformin treatment in pre-adolescent girls thought to be at risk for PCOS reduces the risk and/or the severity of PCOS in later years. It may do this by blocking fat accumulation in the abdomen and liver which seems to set off the insulin resistance. Metformin is not FDA approved for this purpose and as a generic drug there is little profit potential in developing this treatment. I expect it will be many years before preventive therapy for PCOS will come before the FDA for approval .

This information is strictly for educational purposes. Due to high risk of toxicity of medical therapy in young women who can potentially become fertile under treatment for PCOS, no drug should be taken without the close supervision of a physician. The reader agrees to the Terms of Service of this website, metabolism.com

New Diabetes Treatment Guidelines Flawed

New Diabetes Treatment Guidelines Lack Credibility:

Recently the American Academy of Clinical Endocrinologists issued new treatment guidelines for treating Type 2 Diabetes. Complex medical guidelines are often referred to as a treatment algorithm. One of the stated goals of the AACE algorithm is to focus primarily on the theoretical ability of the diabetic medications to control blood sugar while ignoring the cost of the medication. The rationale to this approach is that controlling blood sugar with more expensive drugs will cost less in the long run since patients will be healthier and have less complications due better control of the blood sugar. On the surface this philosophy seems sound but digging beneath the surface reveals dangerous flaws in this thinking.

1. The first assumption, that newer medications for diabetes are better than older drugs is unsubstantiated. In fact there is ample evidence that newer diabetic drugs are no better than the older drugs for controlling blood sugar. The latest study finding no benefit of the newer diabetes medications is the FIELD study conducted outside of the U.S. This study showed that 5 years of treatment with the older diabetic drugs (sulfonylureas, metformin and insulin) resulted in adequate and prolonged control of blood sugar. In 2007 researchers from Johns Hopkins Bloomberg School of Public Health summarized the results of major studies using older and newer anti-diabetic medications and found no significant benefit of the newer medications.

2. The next assumption, that cost is not a key factor in treatment success contradicts most clinicians’ experience in diabetes care. It is clear to me, that patients are far less likely to comply with using expensive drugs than medications they can more easily afford. Looking at the numbers reveals the vast cost differences between the older (generic) versus the newer (brand) medications. Using figures provided by a local pharmacy I found that the retail cost of a typical two drug therapy for diabetes using older drugs is $59 per month. The retail cost of using two of the new drugs for a month ranges from $481 to $570. In more severe diabetes three drugs per day may be needed. The low cost alternative amounts to $185 per month while the high end alternative with new drugs is $610 per month. Looking at the cost of using insulin shows a similar vast cost difference between the older and newer drugs. Older forms of insulin may cost $100 for a month’s supply while a similar course of therapy with the newer insulin preparations will cost almost $250 per month. How many people will be willing and able to afford the new versus the old drugs, particularly knowing that there may be no health benefit to the more expensive drug combination?

The end result of not being able to afford these prices is non-compliance with medications and the result of non-compliance is higher costs passed on to the medical system. The Medco study from 2005 showed that the least compliant patients were more than twice as likely to be hospitalized compared to the most compliant, and that the yearly cost of caring for non-compliant patients is double that of compliant patients.

3. My next point is possibly the most contentious. The AACE guidelines were produced by a committee of physicians chaired by two distinguished endocrinologists, Dr. Paul Jellinger and Dr. Helena Rodbard. Both doctors are highly respected and accomplished. They are also both highly compensated consultants to the pharmaceutical companies which market the newest generation of diabetes medications. In the disclaimer attached to the committee’s recommendations, both Dr. Jellinger and Dr. Rodbard admit to consulting arrangements with virtually every one of the pharmaceutical companies whose interests are effected by their committee’s findings. I too am a consultant to many of these same companies (at least, until now), but I am not responsible for developing national guidelines for diabetes care. In my opinion the close association of both committee chairmen to the pharmaceutical companies detracts heavily from the credibility of their recommendations. The need for credibility is even more important when the AACE committee advises physicians to avoid using sulfonylureas, the only class of drugs not marketed by any of the big pharma companies. and which also happens to be the cheapest drug class, the drugs with the longest history of use, and the class of drugs many regard as the most effective at lowering blood sugar levels. The sulfonylurea class of drugs is so effective at lowering blood sugar, in fact, they are used as the gold standard by which the effectiveness of all new diabetic medications are compared.

4. In contrast with the AACE, the American Diabetes Association (ADA) has issued more conservative guidelines for diabetic therapy, preserving the role of the older generic drugs. My recommendation is that AACE go back to their committee and reconsider the way they have produced their algorithm. Appointing new leadership whose credentials do not lend themselves so readily to skepticism, would be an important first step in that process.

Gary Pepper, M.D.
Editor-in-Chief, Metabolism.com

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