DIRECT Remission of Type 2 Diabetes in Primary Care?
There is no reasonable argument against the fact that excess weight gain is one of the key drivers of diabetes risk, and it should come as no surprise to anyone, that losing weight (though bariatric surgery or otherwise) dramatically improves glycemic control in people living with type 2 diabetes. So what exactly can we learn from the DIRECT study published by Michael Lean and colleagues in The Lancet? For one, this is a large cluster-randomised trial of obesity intervention conducted entirely in a non-specialist primary care setting with significant weight loss (at least 15 Kg) and diabetes remission (defined as glycated haemoglobin (HbA1c) of less than 6·5% after at least 2 months off all antidiabetic medications) as the pre-defined primary outcome at 12 months. In the intervention centres, a nurse or dietitian (as available locally) was given a total of 8 h structured training by the study research dietitians experienced in the Counterweight-Plus program. Initial weight loss was induced with a total diet replacement phase using a low energy formula diet (825–853 kcal/day) for 3 months (extendable up to 5 months if wished by participant), followed by structured food reintroduction of 2–8 weeks (about 50% carbohydrate, 35% total fat, and 15% protein), and an ongoing structured programme with monthly visits for long-term weight loss maintenance. Given the primary care non-specialist setting of this trial, the key findings (as summarized by the authors), were perhaps surprising: “Just less than a quarter of participants in the intervention group achieved weight loss of 15 kg or more at 12 months, half maintained more than 10 kg loss, and almost half had remission of diabetes, off antidiabetic medication….Remission was closely related to the degree of weight loss maintained at 12 months, with achievement in 86% of participants with at least 15 kg weight loss, and 73% of those with weight loss of 10 kg or more. 28% of all eligible individuals volunteered to participate,17 and 79% completed the intensive total diet replacement phase…” In general, the intervention was well tolerated with 117 out of 150 participants (78%) in the intervention group completing the intervention. So here are the key learning from DIRECT: For one, there should no longer be any doubt that “remission” of Type 2 diabetes is possible in a substantial number of patients, if we can help them achieve and sustain significant weight loss – the odds of experiencing remission are directly proportional… Read More »
Oral Semaglutide Is As Effective For Weight Loss As Injections
Readers will recall, that once-weekly injections of the novel long-acting GLP-1 analogue semaglutide was recently shown (in patients with type 2 diabetes) to result in a rather impressive weight loss. Now, a phase II dose-finding study comparing various oral doses of semaglutide to subcutaneous injections in patients with type 2 diabetes was just published in JAMA. The 26-week trial with 5-week follow-up included around 600 patients with type 2 diabetes and insufficient glycemic control using diet and exercise alone or a stable dose of metformin were randomized to once-daily oral semaglutide of 2.5 mg (n = 70), 5 mg (n = 70), 10 mg (n = 70), 20 mg (n = 70), 40-mg 4-week dose escalation (standard escalation; n = 71), 40-mg 8-week dose escalation (slow escalation; n = 70), 40-mg 2-week dose escalation (fast escalation, n = 70), oral placebo (n = 71; double-blind) or once-weekly subcutaneous semaglutide of 1.0 mg (n = 70) for 26 weeks. Mean change in HbA1c level from baseline to week 26 decreased with oral semaglutide (dosage-dependent range, −0.7% to −1.9%) and subcutaneous semaglutide (−1.9%) and placebo (−0.3%); Significant reductions were also seen in body weight with both oral (dosage-dependent range, −2.1 kg to −6.9 kg) and subcutaneous semaglutide (−6.4 kg) vs placebo (−1.2 kg)> Adverse events (largely consisting of mild to moderate gastrointestinal events) were as expected and relatively comparable between the treatment arms. Although this was a diabetes study, these findings clearly hold promise for the further development of an oral formulation of semaglutide for the obesity indication. @DrSharma Tønsberg, Noway Disclaimer: I have served as a consultant for Novo Nordisk, the maker of semaglutide.
Guest Post: Australian GPs Recognise Obesity As A Disease
The following is a guest post from my Australian colleague Dr. Georgia Rigas, who reports on the recent recognition of obesity as a disease by the Royal Australian College of General Practice (RACGP). Last week, the Royal Australian College of General Practice (RACGP) President, Dr Seidel recognised obesity as a disease. The RACGP is the first medical college in Australia to do so. This was exciting news given that we have just observed World Obesity Day a few days ago. According to the Australian Bureau of Statistics1, over 60% of Australian adults are classified as having overweight or obesity, and more than 25% of these have obesity [defined as a Body Mass Index (BMI) ≥30] (ABS2012). Similarly in 2007, around 25% of children aged 2–16 were identified as having overweight or obesity, with 6% classified as having obesity (DoHA 2008). These are alarming statistics. The recent published BEACH data for 2015-162, showed that the proportion of Australian adults aged 45-64yo presenting to GPs has almost doubled in the last 15+ years. Worryingly the numbers are predicted to continue rising, with 70% of Australians predicted to have overweight or obesity by 2025. Embarrassingly, the BEACH data also indicated that <1% of GP consultations centred around obesity management. So obviously what we, as GPs have been doing..,or rather not doing…isn’t working! The RACGP’s General Practice: Health of the Nation 2017 3report found Australian GPs identified obesity and complications from obesity as one of the most significant health problems Australia faces today and will continue to face in coming years as the incidence of obesity continues to rise. But what are we doing about it?…. I think the answer is evident… clearly not enough! Thus, we can only hope that this announcement by the RACGP will have a ripple effect, with other medical colleges in Australia and then the Australian Medical Association following suit. So what does this mean in practical terms? For those individuals with obesity (BMI ≥30) with no “apparent” comorbidities or complications from their excess weight…[though you could argue they will develop (if not already) premature osteoarthritis of the weight bearing joints…..] would be eligible for a chronic care plan [government subsidized access to a limited number of consultations with allied health services] given the chronic and progressive nature of the disease. It also highlights the need for GPs to start screening ALL patients in their practice-young and old; for… Read More »
Weight Change (Not Weight!) Is A Vital Sign
Why do doctors weigh people? Because, very early in medical school, we are taught that body weight is an important indicator of health. While one may certainly argue about the value of a single weight measurement at any point in time (especially in adults), there is simply no denying that weight trajectories (changes in body weight – up or down) can provide important (often vital) clinical information. Let’s begin with the easiest (and least arguable) situations of all – unintentional weight loss. Among all clinical parameters one could possibly measure, perhaps non should be as alarming as someone losing weight without actively trying. In almost every single instance of “unintentional” weight loss, the underlying problem needs to be found, and more often than not, the diagnosis is probably serious (cancer is just one possibility). As with any serious condition, the earlier you detect it, the sooner you can do something about it, therefore, the more often you weight someone, the more likely you will detect early “non-intentional” weight loss. The contrary situation (un-intentional weight gain) is as important. When someone is gaining weight for no good reason, one needs to look for the underlying cause, which can include everything from an endocrine problem to heart failure. On the other hand, weight stability, is generally a sign that things are probably “under control”, as they should be when energy homeostasis works fine and people are in energy balance. Perhaps my own obsession with weighing people comes from my work in nephrology, where we obsess about people’s “dry weight” and use weight as a general means to monitor fluid status. The same is true for working with patients who have heart failure. Note for all of the above, that while a single (random) weight measurement tells you very little (almost nothing) about anybody’s health status, unexplained changes in body weight are one of the most useful and important clinical signs in all of medicine. Obviously, to plot a trajectory, one has to start somewhere, which means that every patient needs to have a “baseline” body weight recorded somewhere in their chart. While this value may not provide any valuable information, the next one may. This is why every single patient needs to be weighed at least once in a clinical setting. As you will imagine, both the context and interpretation of serial weight measurements becomes most challenging in the setting of obesity… Read More »
The Key To Obesity Management Lies In The Science Of Energy Homeostasis
If there is one thing we know for sure about obesity management, it is the sad fact, that no diet, exercise, medication, not even bariatric surgery, will permanently reset the body’s tendency to defend and regain its body weight to its set point – this generally being the highest weight that has been achieved and maintained for a notable length of time. Thus, any effective long-term treatment has to offset the complex neurobiology that will eventually doom every weight-loss attempt to “failure” (no, anecdotes don’t count!). Just how complex and overpowering this biological system that regulates body weight is, is described in a comprehensive review by the undisputed leaders in this field (Michael Schwartz, Randy Seeley, Eric Ravussin, Rudolph Leibel and colleagues) published in Endocrine Reviews. Indeed the paper is nothing less than a “Scientific Statement” from the venerable Endocrine Society, or, in other words, these folks know what they’re talking about when it comes to the science of energy balance. As the authors remind us, “In its third year of existence, the Endocrine Society elected Sir Harvey Cushing as President. In his presidential address, he advocated strongly in favor of adopting the scientific method and abandoning empiricism to better inform the diagnosis and treatment of endocrine disease. In doing so, Cushing helped to usher in the modern era of endocrinology and with it, the end of organo-therapy. (In an interesting historical footnote, Cushing’s Energy Homeostasis and the Physiological Control of Body-Fat Stores presidential address was given in , the same year that insulin was discovered.)” Over 30 pages, backed by almost 350 scientific citations, the authors outline in excruciating detail just how complex the biological system that regulates, defends, and restores body weight actually is. Moreover, this system is not static but rather, is strongly influenced and modulated by environmental and societal factors. Indeed, after reading this article, it seems that the very notion, that average Jane or Joe could somehow learn to permanently overcome this intricately fine-tuned system (or the societal drivers) with will power alone is almost laughable (hats off to the very few brave and determined individuals, who can actually do this – you have climbed to the top of Mount Everest and decided to camp out there for the foreseeable future – I wish you all the best!). Thus, the authors are confident that, “The identification of neuromolecular mechanisms that integrate short-term and long-term control… Read More »
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