Since I started working as a dietitian in 2008, I can’t think of another medication that is comparable to GLP1s in terms of changing disease courses and outcomes. GLP1s are increasingly being used to manage blood glucose levels and assist with weight loss, but there are growing indications to help with cardiovascular outcomes and reduce proteinuria.
But as dietitians, one of the main concerns that I see coming up is how to manage:
- The GI symptoms
- Prevent malnutrition
- Maintain muscle mass and function
So I was excited when a colleague sent me today’s journal club paper:
This is the first of the a 4 part series. This past deals mostly with the background elements of GLP1 therapy. The other posts part of this series are:
- Part 2: How can dietitians manage GI side effects from GLP1s?
- Part 3: How and why do GLP-1s change dietary intake?
- Part 4: What nutrition and lifestyle recommendations should be made for people taking GLP1 therapy?
How many people are taking GLP1s?
According to the authors between 6-12% of Americans are either taking or have taken a GLP1. This number increases in the subset of the population who has been told they have overweight or obesity to 22%. That’s almost 1 in 4!
What are the nutrition concerns with GLP1s?
Similar to my own experience with GLP1s the authors highlight four potential nutrition related concerns with these medications, including:
- GI Symptoms
- Risk of inadequate nutrient intake related to reduced food intake combined with insufficient nutrition counselling
- Low of muscle mass and bone density
- High discontinuation rates related to side effects, costs or patient preferences
- Limited public and clinician knowledge about complementary nutrition and lifestyle changes
What are examples of GLP1s?
GLP1s stands for glucagon-like peptide 1 receptor antagonist. The authors highlight several medications that are covered by this paper, including:
- Semaglutide, in Canada this is marketed as Ozempic
- Liraglutide (marketed as Victoza)
- Tirzepatide (marketed as Mounjaro)
Tirzepatide is technically a combination medication which functions as a traditional GLP1, but also adds a glucose-dependent insulinotropic polypeptide receptor antagonism.
What side effects are anticipated with GLP1s?
Side effects are considered common but mild with GLP1 therapy. According to the authors, most symptoms will occur within the first weeks of initiation and with each dose escalation. The most common side effects are:
- Nausea
- Diarrhea
- Vomiting
- Constipation
- Abdominal pain
What causes side effects from GLP1s?
Causes of side effects can be varied, however the three primary causes are:
- Delayed gastric emptying which can cause bloating, fullness and nausea.
- Activation of several areas of the brain responsible for weight regulation, appetite and nausea.
- For some people GLP1s can also impact intestinal motility and secretions which can lead to diarrhea.
What nutritional deficiencies are associated with GLP1s?
Treatment with GLP1s will result in significant reductions in appetite and energy intake. Reported decreases in energy intake are between 16-39%. Additional GI side effects may also decrease nutrient absorption.
Decreases in energy intake can be associated with inadequate intake of vitamins and minerals, especially for females whose intake falls below 1200kcals and for males whose intake falls below 1800kcals per day. The primary nutrients of concerns include:
- Iron
- Calcium
- Magnesium
- Zinc
- Vitamin A, D, E, K, B1, B12 and C.
What are some signs of nutrient deficiencies to look for?
According to the authors, the key signs of nutrient deficiencies to look out for include:
- Fatigue beyond expected levels
- Excessive Hair Loss
- Skin Flakiness
- Itching
- Muscle Weakness
- Poor Wound Healing
- Unusual Bruising
How much muscle mass is lost with GLP1 therapy?
Rapid weight loss, from any cause, is associated with losses in both fat and muscle mass. In modeling studies weight loss induced by GLP1s is predicted to result in a 10-15% muscle mass loss for females and a 20-25% muscle mass loss for males. It is important to note that these changes are similar to weight loss from other methods including bariatric surgery and very low calorie diets. These changes tend to be more pronounced if accompanied by inadequate protein intake, absence of strength training exercises, and among people with older ages.
How much bone mass is lost with GLP1 therapy?
Bone loss is associated with all types of weight loss, with greater bone loss expected when weight loss is more quick (over 3-4 months) and substantial (>14%). The authors of this article did not quantify how much bone loss is anticipated with GLP1 therapy, but they do not that weight cycling may exacerbate bone losses more.
How many people keep taking GLP-1s after starting?
While clinical studies had reported that as many as 83-88% of people who started these medications stayed on them at the 66-68 week mark, in clinical practice this number is much lower.
Reports are that by 1 year, only about 33-50% of people will still be on a GLP1 and by year 2, that number is as low as 15%.
Why do people stop taking GLP-1s?
People who stop taking GLP-1s tend to be older, above age 65, poor weight response or GI symptoms. There is also speculation that cost is a reason depending on a person’s access to coverage from private insurance companies.
Does taking a GLP-1 save health care costs in the long run?
Theoretically taking GLP-1s could result in health care cost savings with reduced needs for health care use later on. However, to date, all studies suggest that at this point the cost of the GLP-1s outweigh the long term health care savings.
(One side note that I will add – is that given the potential long term savings, it is possible that more time is needed to see true cost effectiveness). However as the authors in the paper point out, the benefits, especially weight loss, is only maintained while people stay on the medication, and given that by year 2 as many as 85% of people have stopped this medication, it is easy to see why current cost-benefit analysis have failed to see significant health care cost savings from these medications.
What health conditions can be exacerbated when starting a GLP-1 for obesity management?
The authors highlight a few conditions to counsel high risk patients about:
1) For those with a history of kidney stones – dietary counseling should include recommendations to avoid high-oxalate foods, highly processed foods and animal proteins.
2) For those at risk of kidney disease, counseling points include ensuring adequate hydration and monitoring changes in kidney function
3) Micronutrient screening should be done for any one at high risk of nutrient deficiencies, example include people with a history of celiac disease, bariatric surgery, inflammatory diseases, or known previous nutrient deficiencies.
4) Eating disorders – the authors acknowledge that very little is known about how GLP-1 use will impact eating disorders, however they recommend that in such cases, ensuring people have adequate supports, including access to an obesity medicine specialist and an eating disorder specialist is recommended.
Want to know more?
Keep reading the next three posts in the series here:
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