From the Guidelines
For a patient with significant weight loss and blood glucose levels not controlled by metformin, a GLP-1 receptor agonist like semaglutide (Ozempic) or liraglutide (Victoza) would be the best next option. This recommendation is based on the most recent and highest quality study available, which suggests that GLP-1 receptor agonists are effective in improving glycemic control while being weight-neutral or promoting weight gain in patients who need it 1.
Key Considerations
- The patient's significant weight loss and uncontrolled blood glucose levels despite metformin therapy indicate the need for a more potent glucose-lowering agent.
- GLP-1 receptor agonists, such as semaglutide or liraglutide, have been shown to be effective in achieving and maintaining individualized glycemic goals, with a low risk of hypoglycemia 1.
- These medications work by increasing insulin secretion in response to meals, suppressing glucagon, and slowing gastric emptying, making them a suitable option for patients with significant weight loss.
Treatment Approach
- Start with a low dose of semaglutide (0.25 mg weekly subcutaneously) and titrate up gradually to 1 mg weekly as tolerated, or begin liraglutide at 0.6 mg daily and increase to 1.8 mg daily.
- Monitor for gastrointestinal side effects like nausea or vomiting, which typically improve over time.
- Ensure the patient is not experiencing weight loss due to undiagnosed conditions like malignancy, hyperthyroidism, or gastrointestinal disorders before starting this medication.
Rationale
- The choice of medication added to metformin is based on the clinical characteristics of the patient and their preferences, with GLP-1 receptor agonists being a preferred option for patients with significant weight loss and uncontrolled blood glucose levels 1.
- The use of GLP-1 receptor agonists has been associated with a reduction in cardiovascular risk factors and improvement in hepatic steatosis, making them a suitable option for patients with type 2 diabetes 1.
From the FDA Drug Label
Patients with inadequately controlled type 2 diabetes on at least 1500 mg per day of metformin and on a sulfonylurea, entered a 2 week open-label placebo run-in. At the end of the run-in, patients who remained inadequately controlled and had an HbA1c between 7% and 10% were randomized to placebo, JARDIANCE 10 mg, or JARDIANCE 25 mg Treatment with JARDIANCE 10 mg or 25 mg daily provided statistically significant reductions in HbA1c (p-value <0. 0001), FPG, and body weight compared with placebo At Week 52, JARDIANCE 25 mg and glimepiride lowered HbA1c and FPG. The difference in observed effect size between JARDIANCE 25 mg and glimepiride excluded the pre-specified non-inferiority margin of 0. 3%. At Week 52, JARDIANCE 25 mg daily resulted in a statistically significant difference in change from baseline for body weight compared to glimepiride (-3.9 kg for JARDIANCE 25 mg vs. +2.0 kg for glimepiride;
The best antidiabetic to start on someone with significant weight loss and BGL not controlled by metformin is empagliflozin (JARDIANCE), as it has been shown to provide statistically significant reductions in HbA1c, FPG, and body weight compared to placebo and glimepiride 2.
- Key benefits of empagliflozin include: + Statistically significant reductions in HbA1c and FPG + Statistically significant reduction in body weight + Non-inferior to glimepiride in terms of HbA1c reduction
- Dosage: 10 mg or 25 mg daily It is essential to note that the decision to start any medication should be made under the guidance of a healthcare professional, taking into account the individual patient's needs and medical history.
From the Research
Antidiabetic Treatment Options
When considering antidiabetic treatment for someone with significant weight loss and blood glucose levels not controlled by metformin, several options can be explored.
- GLP-1 Receptor Agonists: These have been shown to be effective in weight loss and improving glycemic control. Studies such as 3 and 4 highlight the benefits of GLP-1 receptor agonists, including liraglutide and semaglutide, in achieving significant weight loss and improving blood glucose levels.
- SGLT2 Inhibitors: These can also be considered for their glucose-lowering effects and additional benefits of weight loss and blood pressure reduction, as discussed in 4 and 5.
- Combination Therapy: In some cases, combining different antidiabetic medications may be necessary to achieve optimal glycemic control. For example, adding empagliflozin to multiple daily injections of insulin has been shown to improve glucose control, reduce weight, and lower insulin doses without increasing the risk of hypoglycemia, as seen in 5.
Considerations for Treatment Selection
When selecting an antidiabetic treatment, several factors should be considered, including:
- Cardiovascular Risk: GLP-1 receptor agonists have been shown to confer protection against major cardiovascular disease in patients with established atherosclerotic cardiovascular disease, as discussed in 4.
- Renal Function: SGLT2 inhibitors are most effective when the estimated glomerular filtration rate is more than 60 ml per min per 1·73m2 at initiation, and should be avoided where there is a risk of diabetic ketoacidosis, as noted in 4.
- Weight Loss: GLP-1 receptor agonists have been associated with significant weight loss, as seen in 3, 6, and 7.
Potential Side Effects
It's also important to consider the potential side effects of these treatments, such as:
- Gastrointestinal Adverse Events: GLP-1-based therapies can cause gastrointestinal adverse events, including nausea, vomiting, obstipation, or diarrhea, which can often be mitigated by slow up-titration, as discussed in 3.