Why do some patients with Diabetes Mellitus (DM) experience weight loss, while others gain weight?

From the Guidelines

Diabetic patients can experience either weight loss or weight gain depending on the type of diabetes they have, its severity, and the treatments they're using, with the most recent evidence suggesting that modest, sustained weight loss can delay the progression from prediabetes to type 2 diabetes and is beneficial for type 2 diabetes management 1. The reason for this variation in weight trends among diabetic patients is multifaceted. In type 1 diabetes and uncontrolled type 2 diabetes, weight loss occurs because without sufficient insulin, the body cannot use glucose for energy and begins breaking down fat and muscle tissue instead. This process, along with glucose being excreted in urine, leads to calorie loss and weight reduction. Some key points to consider include:

• The importance of weight management in diabetic patients, with a goal of at least 5% weight loss to achieve beneficial outcomes in glycemic management, lipids, and blood pressure 1.
• The use of individualized eating plans resulting in an energy deficit, combined with enhanced physical activity, to support weight loss and improve A1C, CVD risk factors, and well-being in adults with overweight or obesity and prediabetes or diabetes 1.
• The consideration of medication-assisted weight loss for people at risk for type 2 diabetes when needed to achieve and sustain 7-10% weight loss, as well as the potential benefits of metabolic surgery for select individuals with type 2 diabetes 1. Conversely, weight gain often happens in diabetic patients who start insulin therapy or take certain medications like sulfonylureas (glipizide, glyburide), thiazolidinediones (pioglitazone), or insulin secretagogues. These treatments help the body utilize glucose more effectively, which can increase fat storage and fluid retention. Additionally, some patients may gain weight due to defensive eating to avoid hypoglycemia or because improved glucose control reduces the calories lost through glycosuria. The balance between insulin resistance and insulin deficiency plays a crucial role in determining whether a diabetic patient loses or gains weight. Medications like metformin and SGLT-2 inhibitors (empagliflozin, dapagliflozin) may help with weight management, while lifestyle factors such as diet and physical activity remain important for all diabetic patients regardless of their weight tendencies. It is also important to note that maintaining weight loss is challenging but has well-recognized long-term benefits, and that disordered eating, eating disorders, and/or disrupted eating can increase challenges for weight and diabetes management 1.

From the FDA Drug Label

Weight gain: In trials of up to 6 months duration in patients with type 1 and type 2 diabetes, LEVEMIR was associated with somewhat less weight gain than NPH (Table 4). Whether these observed differences represent true differences in the effects of LEVEMIR and NPH insulin is not known, since these trials were not blinded and the protocols (e.g., diet and exercise instructions and monitoring) were not specifically directed at exploring hypotheses related to weight effects of the treatments compared.

The reason for weight loss or weight gain in diabetic patients is not directly explained in the provided drug label. However, it is mentioned that LEVEMIR was associated with somewhat less weight gain than NPH in trials of up to 6 months duration in patients with type 1 and type 2 diabetes 2.

• The clinical significance of the observed differences has not been established.
• The trials were not blinded, and the protocols were not specifically directed at exploring hypotheses related to weight effects of the treatments compared.
• Weight loss is not mentioned in the provided text.
• The provided information does not allow for a clear explanation of why some diabetic patients lose weight while others gain weight.

From the Research

Weight Changes in Diabetic Patients

• Diabetic patients may experience varying weight changes, with some losing weight and others gaining weight, due to several factors 3, 4, 5, 6, 7.
• The presence of insulin resistance, which is strongly correlated with obesity, can contribute to weight gain in diabetic patients 3.
• Certain medications, such as glucagon-like peptide-1 (GLP-1) receptor agonists, can help with weight loss by reducing appetite and improving glucose-dependent insulin release 3, 4.

Factors Associated with Weight Gain

• Baseline factors associated with weight gain in diabetic patients starting on insulin therapy include BMI, A1C, insulin regimen, insulin dose, other glucose-lowering therapies, and hypertension 7.
• A higher A1C at baseline, a higher insulin dose at baseline and at 1 year, and a lower baseline BMI are independently associated with greater weight gain 7.
• Insulin regimen per se is not a predictive factor for weight gain, but the type of insulin and dosage can influence weight changes 7.

Lifestyle Modifications and Weight Changes

• Lifestyle interventions, including dietary changes and physical activity, can significantly improve glycemic control and lead to weight loss in diabetic patients 6.
• Strategies combining individualized and group-based activities are the most effective in achieving weight loss and improving glycemic control 6.
• Weight loss is consistently observed with lifestyle interventions, particularly when combined with standard care 6.

Medications and Weight Changes

• GLP-1 receptor agonists can reduce body weight, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors are body weight neutral 4.
• The use of premixed insulin, metformin, and a GLP-1 receptor agonist as combination therapy can improve glycemic control and lead to weight loss in diabetic patients 5.
• The choice of medication and dosage can influence weight changes, and healthcare providers should consider individual patient factors when selecting therapies 3, 4, 5.