Too many patients, as documented in an on-line study of 12,000 individuals conducted by the American Thyroid Association published in June 2018, (https://doi.org/10.1089/thy.2017.0681) , complain of persistent symptoms of hypothyroidism despite what their doctors believe is successful treatment with levothyroxine (brands include Synthroid, Unithroid, Tirosent, Levoxl). We believe something needs to be done to resolve this conflict between patients and their doctors.
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.
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?
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.
(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.
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.
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 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 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 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.
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.
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