May 2023: Weight Management and Diabetes Medications (Part 2)

May 2023: Weight Management and Diabetes Medications (Part 2)

Lilly logoWe are pleased to present the second in a three-part series on weight management and diabetes sponsored by Lilly and written by Amy Hess Fischl, MS, RD, LDN, BC-ADM, CDCES. Content is provided for information only; please consult with your healthcare provider before making changes to your diabetes management.

In the first article in this series, we discussed weight management as a tool for attaining in-range blood sugar. This second part will cover diabetes treatments and medications available to help lower excess weight. Our main topics will include lifestyle changes as a first line and continued treatment; understanding the impact that current diabetes medications have on weight and adding medications that aid in weight loss; and surgical options. This information is an overview since each topic could be an entire article alone! The point is to understand the basics and then delve into more details on your own or with your healthcare team.

Body Mass Index (BMI) is one of the screening tools used to determine the amount of body fat an individual has based on their height and weight. In general, the following BMI ranges (in kg/m2) classify different weight types:

  • Underweight: Less than 18.5
  • Optimum range: 18.5 to 24.9
  • Overweight: 25 to 29.9
  • Class I obesity: 30 to 34.9
  • Class II obesity: 35 to 39.9
  • Class III obesity: More than 40

Although a BMI of at least 25 kg/m2 is considered overweight, an increasing amount of data over the years shows that a BMI of over 23 kg/m2 in patients of South Asian, Southeast Asian, and East Asian genetic heredity is considered overweight. Health risks associated with overweight and obesity typically are observed at lower BMIs in these populations.1 Close to 80-90% of people with type 2 diabetes are overweight or obese. We are also now finding that 62% of adults with type 1 diabetes had overweight or obesity, which is similar to the 64% rate seen among the general population. However, only about half of these patients received lifestyle recommendations from providers or engaged in lifestyle modification. Weight management in type 1 diabetes is complicated by insulin use. Food intake and physical activity changes often require insulin timing and dosage adjustments to prevent hypoglycemia. Evidence-based guidance on lifestyle modification in type 1 diabetes remains sparse, potentially contributing to low rates of recommendation by providers and low engagement by patients.2 Treatment options should be decided upon based on the individual's BMI as well as their ability to follow the requirements needed to make the treatment successful.

The table below includes the current treatment recommendations based on BMI.

    BMI category (kg/m2)  
Treatment      25.0-26.9      27-29.9        >=30       
Lifestyle – meal plan changes, physical activity, behavioral counseling X X X
Medication   X X
Surgery     X

 

When considering the time and effort required to achieve weight loss goals successfully, it is essential to remember that as little as 3–7% weight loss may reduce diabetes risk or may increase glucose time-in-range for those with diabetes.3

Nutrition, physical activity, and behavioral therapy to achieve and maintain >5% weight loss are recommended for most people with type 2 diabetes and overweight or obesity.3 Because an energy deficit is required for weight loss, reducing caloric intake forms the foundation of any weight-loss strategy.1 A structured and comprehensive lifestyle intervention program designed for weight loss (lifestyle therapy) that includes a healthy meal plan along with calorie reduction, physical activity, and behavioral intervention is recommended for all individuals with diabetes with overweight or obesity seeking to lose weight. This is the foundation of ALL weight loss strategies, meaning before someone has any hope of finding long-lasting success with any other option, you must first have a firm grasp of these skills. There are no shortcuts for weight loss that are sustainable. Sure, you can achieve weight loss rapidly, but it does not mean the weight loss is permanent. Behavior change skills in relation to how and why you eat are crucial to set the stage for further success. To put things into perspective and to lay out the effort required, most weight management programs include 14-16 sessions with a registered dietitian nutritionist (RDN) over three to twelve months. Based on the literature, the average weight loss attained is approximately 8 kg or 5-8% of total body weight.4

Every major organization, including the American Diabetes Association, the American Association of Clinical Endocrinologists, and the American Gastroenterological Association, suggest the use of medications for overweight/obesity for those with diabetes. In this article, we will only focus on the impact of diabetes medications on weight loss. Of the diabetes medications available and frequently used in the US, metformin, sodium glucose co-transporter 2 inhibitors, and glucagon like peptide-1 receptor agonists (GLP-1 RAs) promote weight loss. Dipeptidyl peptidase-4 inhibitors and fixed-ratio insulin/GLP-1 RA combination therapies appear to have no impact on weight. Thiazolidinediones, insulin secretagogues (sulfonylureas, meglitinides), and insulins are associated with weight gain. Sulfonylureas are additionally associated with a higher risk of serious hypoglycemia from hyperinsulinemia, making them less suitable for those who are overweight or have obesity. We also find that many people are over-titrated on basal insulin, resulting in an increased risk of hypoglycemia and weight gain without achieving glycemic goals. It is important to have a discussion with your healthcare provider about the medications you are taking and how they may affect your weight loss efforts.5

Current diabetes medications that are approved for use in type 2 diabetes and can be used to aid in reducing weight. The information provided is based on the use of the medication as monotherapy at maximum dosage:

Name Type A1C reduction Weight loss achieved Side effects
metformin Oral medication—once-three times per day with meals -1.5% -2.4 kg Stomach upset, diarrhea
SGLT-2 agonists        
Canagliflozin (Invokana) Oral medication once daily -1.03% -3.9 kg Urinary tract infections, increased urination
Dapagliflozin (Farxiga) Oral medication once daily -0.9% -2.7 kg Female genital fungal infections, urinary tract infections, increased urination
Empagliflozin (Jardiance) Oral medication once daily -0.8% -3.2 kg Urinary tract infections, female genital fungal infections, increased urination
Ertugliflozin (Steglatro) Oral medication once daily -0.8% -2.1 kg Female and male genital fungal infections, urinary tract infections
GLP-1 agonists        
Dulaglutide (Trulicity) Injected once weekly -0.8% -2.3 kg Nausea, diarrhea, vomiting

Exenatide (Byetta)
Exenetide XR (Bydureon)

Injected twice per day
Injected once weekly

-1.03%
-1.39%
-1.4 kg Injection site nodules, nausea
Liraglutide (Victoza) Injected once daily -1.1% -2.5 kg Nausea, diarrhea, headache
Semaglutide (Ozempic) Injected once weekly -1.6% -4.7 kg Nausea, vomiting, diarrhea
Semaglutide (Rybelsus) Oral medication once daily -1.4% -3.7 kg Nausea, abdominal pain, diarrhea
Tirzepatide (Mounjaro) Injected once weekly -1.7% -7.8 kg Nausea, diarrhea

Information compiled based on the references below for all products in the table:
Curr Obes Rep. 2019 June ; 8(2): 156–164. doi:10.1007/s13679-019-00335-3.
https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/INVOKANA-pi.pdf
https://www.farxiga.com/
https://content.boehringer-ingelheim.com/DAM/7d9c411c-ec33-4f82-886f-af1e011f35bb/jardiance-us-pi.pdf
https://www.merck.com/product/usa/pi_circulars/s/steglatro/steglatro_pi.pdf
https://pi.lilly.com/us/trulicity-uspi.pdf
https://www.bydureon.com/bydureon-bcise.html
https://www.novo-pi.com/victoza.pdf
https://www.novo-pi.com/ozempic.pdf
https://www.novo-pi.com/rybelsus.pdf
https://pi.lilly.com/us/mounjaro-uspi.pdf?s=pi

The above medications are considered off-label for those with type 1 diabetes and may be denied as a form of treatment or will not be covered by insurance. When considering the use of GLP-1 agonists, it is important to understand the possible weight regain that can occur if the medications are discontinued. The STEP 1 extension trial, using semaglutide, included 327 participants. The average weight loss over the 15-month study was 17.3%. Following treatment withdrawal, the participants regained 11.6%. What was also interesting in the study is that any heart-related improvements seen from taking the GLP-1 agonist were also lost. To maintain the benefits of these medications, they do need to be taken indefinitely.6

Metabolic surgery, also termed bariatric surgery, is typically reserved for those individuals with diabetes who have a BMI >30 kg/m2. An extensive evaluation is conducted to determine if someone is appropriate. Even before the surgery, the individual must complete pre-requisite nutrition education and behavioral health interventions. Below are the most common surgical options:7

Procedure Weight loss Side effects
Laparoscopic adjustable gastric banding 20-25% Band erosion
Slip/prolapse
Sleeve gastrectomy 25-30% Leaks difficult to manage
Little data beyond 5 years
20%-30% GERD
Roux-en-Y gastric bypass 30-35% Few proven revisional options for weight regain
Marginal ulcers
Internal hernias possible
Long-term micronutrient deficiencies
Biliopancreatic diversion with duodenal switch 35-45% Malabsorptive
3%-5% protein-calorie malnutrition
GERD
Potential for hernias
Duodenal dissection
Technically challenging
Higher rate of micronutrient deficiencies than roux-en-Y gastric bypass

 

The information above merely scratches the surface regarding the diabetes treatments and medications available to lower excess weight. We must remember that each option builds onto the other. Ongoing lifestyle changes are necessary for medications and surgical options to be successful.

References:
1 Am J Manag Care. 2022;28:S288-S296.
2 Annals of Internal Medicine, 2023. https://www.acpjournals.org/doi/10.7326/M22-3078
3 Diabetes Care 2023;46(Suppl. 1):S128–S139 | https://doi.org/10.2337/dc23-S008
4 Gastroenterology, 2017;152(7):1752-1764; https://doi.org/10.1053/j.gastro.2017.01.045
5 Diabetes Care 2023;46(Suppl. 1):S140–S157 | https://doi.org/10.2337/dc23-S009
6 Diabetes Obes Metab. 2022;24:1553–1564
7 Am J Manag Care. 2022;28:S288-S296

 

Amy Hiss FischlAmy Hess Fischl, MS, RD, LDN, BC-ADM, CDCES, is an advanced practice dietitian and diabetes care and education specialist at the University of Chicago within the departments of pediatric and adult endocrinology. She speaks internationally on all diabetes topics, especially meal plan options for type 1 diabetes, insulin pumps, and continuous glucose monitors. She is actively involved in the American Diabetes Association, the Academy of Diabetes Care and Education Specialists, and the Academy of Nutrition and Dietetics, as well as several international groups for diabetes and pre-diabetes. She was named 2018 IL AADE Diabetes Educator of the Year and also received the 2018 Pan Arab Congress on Diabetes Award of Excellence for her contributions to diabetes care and education. Her dream vacation always includes diving with sharks.