Weight Loss is (Almost Always) More Important than Glucose Control – Diabetes Daily

Experts increasingly agree that weight loss is more important than glucose control for people with type 2 diabetes. Top researchers from around the globe underlined this point in speech after speech at the recent Scientific Sessions diabetes conference.

And in a potentially major shift, the two major diabetes authorities from the United States and Europe unveiled a co-authored draft of new guidelines for diabetes treatment that elevated weight management to “co-primary” status with glucose control.

The Debate That Wasn’t a Debate

Perhaps the most illustrative moment of the conference was billed as a debate between two experts on the superiority of glucose control versus weight loss for type 2 diabetes. But the resulting exchange couldn’t be called a debate at all, because both experts agreed to favor weight loss.

Dr. Jeffrey Mechanick, MD, of New York’s Mount Sinai hospital, supposedly present to argue in favor of blood sugar control, gladly conceded that “in the overwhelming number of cases, weight control is the most important target.”

His “opponent,” Dr. Ildiko Lingvay, MD, MPH, MSCS, made the bulk of the case in favor of prioritizing weight loss. Dr. Lingvay, an endocrinologist at the University of Texas Southwestern, has authored an influential paper on the same subject, and both her paper and her speech were frequently cited by other experts throughout the conference.

Her case, in brief: if you have type 2 diabetes and you lose weight, not only will it improve your blood sugar levels, but it will improve almost everything else about your health, too. For most patients with type 2 diabetes, weight loss addresses the totality of the metabolic condition.

Dr. Lingvay referred to a raft of studies showing extremely strong relationships between weight loss and glycemic improvements, including the probability of remission, as well as improvements in blood pressure, cholesterol, cardiovascular disease risks, and even quality of life. She asserted that weight loss is essentially a “holistic approach to diabetes treatment.”

By contrast, strict glucose control doesn’t necessarily result in those important secondary benefits, and may even backfire when it is achieved primarily through pharmaceutical intensification.

Diabetes Authorities to Prioritize Weight Loss

The magnitude of this shift in treatment philosophy was significantly underscored by the unveiling of a new draft of guidelines for the treatment of hyperglycemia in type 2 diabetes. This annual consensus report, officially co-authored by the American Diabetes Association and the European Association for the Study of Diabetes, exerts a massive influence on the way that diabetes is treated throughout the world.

The new provisional document, presented towards the end of the conference by a constellation of international researchers, was clearly informed by the shift that leading scientists have made away from the glucocentric approach. As Dr. Chantal Mathieu, MD PhD, stated: “We have put weight management to the front of the management of people living with type 2 diabetes.”

Another presenter, Dr. Vanita Aroda, MD, explained that “glycemic management and weight management are really two co-primary goals.”

The centerpiece of the guidance is a decision tree or flowchart that helps medical professionals decide how to treat their patients. The previous and still-operative version of this graphic can be found on page S134 of this PDF. (The new draft is still subject to revision; the final draft will be released during the EASD’s annual conference in September.)

The new flowchart, which audience members were asked not to photograph, will emphasize weight loss to a much greater degree, even including a panel that ranks glucose-lowering drugs by their efficacy for weight loss.

Several presenters urged doctors to seriously consider the weight side effects of different medications. As Dr. Geltrude Mingone, MD, PhD, stated: “When considering glucose-lowering medications, we should consider always the dual action: improving glycemic control but also weight loss.”

As a result, we might expect that clinicians will begin to turn away from glucose-lowering drugs that are associated with weight gain, including sulfonylureas and insulin.

Authorities to Recommend Rapid Treatment Intensification

As in previous versions, the new draft guidance establishes diet, exercise, and lifestyle adjustments as the first and most important approach to treating type 2 diabetes. But in clinical trials, sustainable lifestyle interventions only produce modest weight loss, and in the real world, most diets fail.

The new emphasis on weight loss therefore inevitably means a more serious official push for the only two thoroughly validated weight loss treatments: bariatric surgery and the new generation of weight-loss diabetes drugs.

These drugs – diabetes medications with powerful anti-obesity effects, particularly semaglutide and tirzepatide – have truly altered what diabetes experts think is possible. In a separate session, Dr. Sean Wharton, MD, PharmD, announced that “Sustained weight loss without surgery was a unicorn until recently … the game has changed. Effective obesity management is here.”

Several experts throughout the conference advised that doctors should be prescribing more medication, and doing it sooner, too. The new draft guidance will recommend that doctors now consider “combination therapies” as a first-line treatment, opening the door for more patients to add a second medication (in addition to metformin) at the very moment that they are diagnosed.

In a presentation on diabetes drugs and “therapeutic inertia,” Dr. Carol Wysham, MD, noted that only a tiny percentage of patients that could be using GLP-1 receptor agonists – one class of diabetes drugs with impressive anti-obesity effects – are actually using them. Most doctors, in her view, wait too long before increasing dosage or adding new medications.

The call, from both independent experts and authorities alike, was clear: more people with type 2 diabetes should be using more drugs, specifically those with positive weight loss effects.

The new ADA/EASD guidance also places an emphasis on the importance of cardiovascular and kidney care – a recommendation that might also lead to more aggressive use of diabetes drugs other than metformin, especially GLP-1 receptor agonists and SGLT-2 inhibitors.

Unfortunately, many of these highly effective treatments will likely remain out of reach for most patients, at least in the near future. Bariatric surgery is expensive and intense, and insurers are not prepared to pay for just anyone to get it. And as of today, only one of the new generation of high-dose weight-loss drugs is available in the United States: Wegovy. Demand has overwhelmed production so significantly that the maker has paused all of its marketing efforts.

Dr. Lingvay believes that evidence will mount proving that these pricey therapies are cost-effective, and in the future insurers will be eager to pay for them. But for now, many patients with diabetes will be left without any clear way to follow the new recommendations, except to double down on lifestyle adjustments. Dr. Geltrude Mingone suggested that “very low-calorie diets and meal replacement” should be considered for patients unable to lose weight through general diet and exercise.

Does Everyone with Type 2 Diabetes Need to Lose Weight?

The experts agree: Almost anyone with type 2 diabetes and adiposopathy would benefit from concentrating on weight loss.

What is adiposopathy? It’s a newer term that does not refer specifically to a certain amount of excess weight, but rather to the presence of excess weight that causes ill health effects. Dr. Lingvay strongly prefers it to “obesity.” She repeatedly stated that it is not just the amount of extra weight that matters, but also “abnormal fat distribution and abnormal fat function.” Adiposopathy indicates some dysfunction in fat amount, distribution, and function.

Several experts at the conference agreed that the term “obesity” is now so freighted with stigma and misunderstanding that it should be avoided. That’s especially true in discussions of diabetes onset and progression, where a sharp focus on the amount of excess fat can actually be misleading.

Dr. Lingvay repeatedly stressed her belief that BMI is hopelessly flawed. She furthermore stated that waist-to-height ratio – a measure often believed to be superior to BMI for gauging the amount of excess body fat most associated with cardiometabolic risk – was “much better than BMI,” but still inadequate. Instead, she believes that doctors should rely on a visual examination, coupled with their experience and judgment: “For lack of a better measure, I think our clinical evaluation is the best way we can get to a diagnosis.”

Weight Loss Targets

Dr. Lingvay said that for significant health benefits, patients should target losing “at least 10%” of their overall weight. That is to say, if you weigh 200 pounds, your new goal weight should be 180 pounds – or lower. “After 10%, it’s the more, the merrier.”

Most studies, Dr. Lingvay explained, show that a weight loss in the range of 10-20% “seems to be the sweet spot for achieving most of the benefits.” With that amount, diabetes remission is a possibility, although patients with a longer duration of diabetes are less likely to achieve remission.

Dr. Lingvay, who gave her address before the ADA/EASD presented their new draft on treatment standards for type 2 diabetes, advocated for a more extreme shift of priorities. She suggested that the American Diabetes Association should scrap its official blood sugar target for type 2 diabetes – “an A1C goal for many nonpregnant adults of <7% (53 mmol/mol) without significant hypoglycemia is appropriate” – and replace it with a goal of > 15% weight loss.

“15% weight loss is your new 7% A1C that you should be shooting for.”

Exceptions to the Rule

So, who is the rare type 2 diabetes patient that wouldn’t enjoy wholesale health improvements from weight loss? Dr. Lingvay estimated that perhaps 10-20% have no adiposopathy, individuals that do not show any evidence of abnormal fat amount, distribution, or function. These patients would likely benefit more from an approach that prioritizes blood sugar control.

It’s important to note, however, that while a substantial minority of people with type 2 diabetes are not obese, many of them still have some measure of adiposopathy and could benefit from weight loss. The recent ReTUNE trial has shown that even leaner people with type 2 diabetes can achieve remission through weight loss. And Dr. Lingvay highlighted trials that showed that non-obese patients still benefit from bariatric surgery.

To be clear, no expert at the conference said that blood sugar should be ignored, and in cases of acute hyperglycemia, it is important to first address high blood sugar before worrying about weight loss. Dr. Mechanick also stated that glycemic control should be the priority in patients more likely to suffer negative consequences due to hyperglycemia, a group that might include patients at a high risk of (or already experiencing) microvascular complications such as kidney disease.

Additionally, experts seem nervous about recommending dramatic weight loss for elderly patients, due to the potentially negative complication of sarcopenia (muscle loss).

Dr. Mechanick emphasized that blood glucose improvements be “a primary target of type 2 diabetes treatment, but not the primary target.”

“There are lots of shades of gray.”

Takeaways

The new generation of effective anti-obesity diabetes drugs, high-dose semaglutide and tirzepatide, have made weight loss seem like a newly realistic goal. (Bariatric surgery remains a similarly effective therapy). As a result, leading diabetes experts are pivoting away from their former emphasis on glucose control and are now recommending that weight loss should be the single most important health target for patients with type 2 diabetes.

Diabetes authorities at the ADA and EASD have moved, somewhat more cautiously, in the same direction. They are set to announce that weight control is an equivalent priority to glucose control.

Most people with type 2 diabetes can benefit greatly from weight loss, even many of those without obesity. Weight loss drives blood sugar improvements itself, and also may confer comprehensive long-term health benefits. However, the most effective weight-loss therapies are expensive and are not yet widely available.



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Read more about A1c, American Diabetes Association (ADA), EASD, exercise, GLP-1, glucose, insulin, Intensive management, low blood sugar (hypoglycemia), metformin (Glucophage), obesity, remission, SGLT-2, weight loss.

Author: Mabel Freeman