Background
Visceral and ectopic fat are key drivers of adverse cardiometabolic outcomes in obesity. We aimed to evaluate the effects of injectable liraglutide 3·0 mg daily on body fat distribution in adults with overweight or obesity without type 2 diabetes at high cardiovascular disease risk.
Methods
In this randomised, double-blind, placebo-controlled, phase 4, single centre trial, we enrolled community-dwelling adults, recruited from the University of Texas Southwestern Medical Center, with BMI of at least 30 kg/m
2 or BMI of at least 27 kg/m
2 with metabolic syndrome but without diabetes and randomly assigned them, in a 1:1 ratio, to 40 weeks of treatment with once-daily subcutaneous liraglutide 3·0 mg or placebo, in addition to a 500 kcal deficient diet and guideline-recommended physical activity counselling. The primary endpoint was percentage reduction in visceral adipose tissue (VAT) measured with MRI. All randomly assigned participants with a follow-up imaging assessment were included in efficacy analyses and all participants who received at least one dose of study drug were included in the safety analyses. The trial is registered on
ClinicalTrials.gov:
NCT03038620.
Findings
Between July 20, 2017 and Feb 21, 2020 from 235 participants assessed for eligibility, 185 participants were randomly assigned (n=92 liraglutide, n=93 placebo) and 128 (n=73 liraglutide, n=55 placebo) were included in the final analysis (92% female participants, 37% Black participants, 24% Hispanic participants, mean age 50·2 years (SD 9·4), mean BMI 37·7 kg/m2). Mean change in VAT over median 36·2 weeks was −12·49% (SD 9·3%) with liraglutide compared with −1·63% (SD 12·3%) with placebo, estimated treatment difference −10·86% (95% CI −6·97 to −14·75, p<0·0001). Effects seemed consistent across subgroups of age, sex, race–ethnicity, BMI, and baseline prediabetes. The most frequently reported adverse events were gastrointestinal-related (43 [47%] of 92 with liraglutide and 12 [13%] of 93 with placebo) and upper respiratory tract infections (10 [11%] of 92 with liraglutide and 14 [15%] of 93 with placebo).
Interpretation
In adults with overweight or obesity at high cardiovascular disease risk, once-daily liraglutide 3·0 mg plus lifestyle intervention significantly lowered visceral adipose tissue over 40 weeks of treatment. Visceral fat reduction may be one mechanism to explain the benefits seen on cardiovascular outcomes in previous trials with liraglutide among patients with type 2 diabetes.
Funding
NovoNordisk.
As an Anthropologist I first look at who funded the study, like most of these studies, they are funded by the makers of the drug in question. But I am not a fan of Liraglutide so it doe snot matter and I will give free publicity to Semaglutide which is once a week injection.
Regardless of the above prejudice I can tell you that all these new studies coming out are exciting.
Our understanding of Obesity has gained much scientific ground in the last fifteen years.
While there is a connection between body weight and some of the metabolic consequences associated with it: Mainly Diabetes and its complications, I felt that there was something in the metabolism that alters quickly with increasing body weight which to us at that time was neither measurable or treatable.
Fifteen years ago, a colleague of mine, a Native American Indian, had gastric bypass surgery (which may not be necessary in the future at the rate of scientific advances in obesity metabolism research), had her diabetes dysfunction disappear even before she left the hospital, even before an ounce of weight loss was registered. I thought: this surgery has disrupted a pathway in our guts that gave rise to the metabolic dysfunction.
My own thinking at the moment to prevent Consequences of Obesity is as follows
Obesity is obviously an end result of a conglomeration of human activities in which mind and spirit are involved (to which no attention is paid in the western medical concept)
As this paper shows, visceral and ectopic fat plays an important part in the metabolic dysfunction that we see: Sugar, Cholesterol, Heart and Thyroid dysfunction and many other abnormalities.
This was achieved by a medication with the manipulation of a secreted protein in the gut GLP-1RA
Metabolic consequences of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are the result of enhanced glucose-stimulated insulin secretion, inhibition of glucagon release, delayed gastric emptying and increased satiety.
Obviously this paper is about people who did not have diabetes, so there are other actions which these medications are capable of.
Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion.
Highlights
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LPS induce GLP-1 secretion from L cells through a TLR4-dependent mechanism
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Gut ischemic injury is coupled to immediate GLP-1 secretion in mice and humans
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L cells are mucosal sensors of LPS after gut injury
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GLP-1 secretion is closely related to gut inflammation
Thus an increase in GLP 1 activity acts to repair the Gut and work against the Inflammation.
Now thinking like an anthropologist, where do most of our inflammation come from ? Environment which includes NUTRITION..
There is so much to learn. When I began talking about inflammation to my medical colleagues (an advantage of being an anthropologist is that you are able to interpret ways of thinking of people and if using Derrida's deconstruction, we can even say why a doctor says what he says), they truly made fun of me, because to them Diabetes and Obesity being Inflammatory diseases was unthinkable, this is not Rheumatoid Arthritis they told me.. well every thing comes around..
Diabetes and Obesity are Social Diseases
Underlying Metabolic dysfunction may be Inflammation
and just Medicine alone alleviate a social problem, you need social, cultural and spiritual elements to Nutrition as well as what people call Lifestyle which I would define as Quality of Life.
When the study of weight loss with Semaglutide was published, saying that 40 per cent of the participants lost 18% of their body weight and that they could guarantee at least 5% of the body weight loss, and they were elated, the anthropologist would ask: what made the other 60 per cent not loose 18% of their body weight.
Here I think, a cultural and nutritional approach to their eating habits, a genetic and microbiome way of thinking of what is good for individuals rather than a blanket nutritional prescription of calories and components (so so old fashioned) for a diverse population that is our western world.
Once we understand the Inflammation caused by Nutrition, the social and cultural nature of postprandial blood sugar, a little help from medications at least for a while (I have patients who have reversed their Type 2 Diabetes with weekly injections of GLP 1 RA medications and gone off them when they achieved flat post prandial glucose responses).. the future of metabolic medicine which includes Obesity looks very exciting indeed ..
