Efficacy and Tolerance of Liraglutide for Weight Loss in Obese Type 2 Diabetic Hemodialysis Patients
Status:
Recruiting
Trial end date:
2022-07-17
Target enrollment:
Participant gender:
Summary
Diabetes is the second leading cause of end stage renal disease in France (22% in the 2016
REIN register). In hemodialysis, its prevalence is higher, between 30-40% depending on the
study. Associated with type 2 diabetes, a large number of patients present with overweight
(body mass index or BMI> 25 kg / m2) which can lead to a temporary contraindication to kidney
transplant by the surgeon, or even definitive once BMI is over 30 kg / m2. Indeed, above this
threshold, patients are exposed to an increased risk of surgical complications (wall
infections, suture release), hospitalizations and potentially transplant failure. A recent
study based on the Kidney Registry showed that patients with a BMI> 31 kg / m2 were more
likely to stay on dialysis than to benefit from a transplant whereas for each decrease of 1
kg / m2 of BMI, there is a 9-11% increase in the likelihood of being transplanted. The
management of obesity in dialysis patients is important for reducing cardiovascular risks but
also because it increases the chances of access to transplantation. However, current weight
loss programs are disappointing. The changes in hygiene and diet rules integrated into a
specialized monitoring program only allow a weight loss of 2 to 8% in 24 months for half of
the patients. Bariatric surgery is, of course, a more effective alternative, but with a 10%
risk of postoperative complications.
Glucagon-Like Peptide 1 (aGLP1) analogues are a new class of antidiabetic drugs that have
revolutionized the management of type 2 diabetes. In fact, they combine efficacy on glycemic
control but also on weight loss. They are used in obese non-diabetic people in some
countries, with a reduction in weight of up to 10 to 15% with certain molecules. In addition,
they have shown an effect on reducing cardiovascular events in diabetics including with
Chronic Kidney Disease CKD 3-4. AGPL1 are well tolerated with side effects mainly of
digestive tropism such as nausea or vomiting. Exceptionally, these effects can occur from the
first injection requiring permanent discontinuation of treatment. In 20% of cases, these side
effects can appear in the first weeks. They gradually fade, spontaneously or after
symptomatic treatment and allow titration of the drug.
AGLP1 is currently contraindicated in patients with reduced renal function, that is, when the
glomerular filtration rate (GFR) is <15 ml / min (MRC stage 5-5D), because this population
specific was excluded from the originator studies. However, aGLP1 are small peptides that are
not eliminated by the kidneys. Their elimination takes place through the general catabolism
of proteins. To date, 2 publications have evaluated the safety profile and efficacy of an
aGLP1, liraglutide (Victoza®), in diabetic dialysis patients. These studies showed that the
24 hour plasma concentration of liraglutide increased by 50% over the long term. The safety
profile was acceptable with, as expected, a predominance of gastrointestinal effects in the
first weeks of treatment such as nausea, vomiting. The authors suggest an adjustment of the
dosages and a longer titration period to limit side effects. However, treatment with aGPL1 is
effective with better glycemic control and an average weight loss of 2.6 kg over a period of
3 months. Studies show that weight loss under liraglutide continues beyond 3 months with
possible losses between 4 and 8 kg at 6 months and 12 months of treatment followed 12.
Liraglutide (Victoza®) is the analogue of GPL1 for which we have a sufficiently long
follow-up (> 10 years) on its effectiveness and its short and long-term side effects.
The main objective of this project, in type 2 diabetic patients on dialysis, as a temporary
contraindication for transplant due to overweight, is on the one hand to study the effect of
liraglutide on weight loss and control of diabetes, and on the other hand to assess its
tolerance in this population. The expected benefit is to be able to facilitate registration
on the waiting list and access to renal transplantation of these overweight patients, without
having to resort to more invasive methods such as bariatric surgery.