Objectives are to develop a comprehensive care plan for a person living with diabetes and obesity, outline strategies for minimizing medications that promote excess weight in people with type 2 diabetes, and to discuss additional AOM therapies as adjuncts for weight and glycemic reduction. When caring for patients with type 2 diabetes and obesity, there are several factors to consider. First, it's essential to perform a thorough medication inventory. We want to identify medications that may contribute to weight gain or that may lead to weight loss. Once identified, the clinician must engage other members of the care team to determine if and how weight-promoting medications may be safely stopped or adjusted, and how weight loss medications may be added. This is a short list of medications often associated with weight gain. In terms of antihypertensives, non-selective beta blockers are the biggest offenders. Antipsychotics are a major category associated with weight gain. Ziprazidone is typically the antipsychotic with minimal weight gain. Some tricyclic antidepressants and SSRIs can also contribute to weight gain. Fluoxetine and bupropion are typically the weight-neutral options in this category. Multiple antiepileptics can be weight-promoting as well as antiretrovirals, such as protease inhibitors. In terms of contraceptives, typically older combination contraceptives with higher doses of estrogen are associated with weight, as are injections such as Depo-Medroxyprogesterone acetate. Glucocorticoids in any form are weight-promoting. Clinicians often screen for oral glucocorticoid use, but may miss injections that are more difficult to track in the electronic medical record. Similarly, assessing over-the-counter medication use is challenging. Use of antihistamines and various supplements is important to identify. There are several medications in the antidiabetic category that can be associated with approximately 2-4 kg of weight gain. TZDs can cause edema as well as affect adipose tissue distribution. Sulfonylureas are similarly associated with weight gain. Sulfonylureas are also higher risk for hypoglycemia when compared to other agents used for diabetes management. During periods of hypoglycemia, additional caloric intake occurs, which can of course lead to weight gain. When treating both diabetes and obesity, weight-neutral medications and medications associated with weight loss are the preferred agents. Dipeptidyl-dipeptidase-4 inhibitors, or DPP-4 inhibitors, are in the weight-neutral category. Metformin is generally weight-neutral, though some individuals do experience some weight loss with metformin. Sodium glucose cotransporter-2 inhibitors, or SGLT2 inhibitors, are associated with weight loss. Even more weight loss is reported with the use of glucagon-like peptide 1 receptor agonists, or GLP-1s, and glucose-dependent insulinotropic polypeptide glucagon-like peptide 1 receptor agonists. To summarize the oral and injection options for type 2 diabetes from neutral to very high amounts of weight loss expected, we start with DPP-4 inhibitors in the weight-neutral category, proceed to metformin, then to SGLT2 inhibitors, with which weight loss is expected. Finally, our newer agents, GLP-1 receptor agonists and dual GIP-GLP-1 receptor agonists are associated with the highest amounts of weight loss. I'll now review a case to highlight some principles of management. A 55-year-old male with type 2 diabetes, hypertension, and chronic kidney disease presents for diabetes management. Medications for diabetes include insulin, glargine, 50 units nightly, pioglitazone, 30 mg daily, metformin, 850 mg twice a day, and glifazide, 5 mg twice a day. BMI is 36.5, hemoglobin A1c is 7.5%, labs are otherwise notable for random glucose of 300 and EGFR of 55. Let's outline strategies to mitigate weight gain and optimize glycemic control. When assessing glycemic control, the first step is to collect data. When possible, a continuous glucose monitor, or CGM, will provide the most data. If a personal CGM is not possible, temporary placement of a professional CGM can also be useful. Otherwise, frequent finger stick monitoring will provide information beyond the hemoglobin A1c. This is particularly important in our case, as our patient has a discordant hemoglobin A1c and random blood sugar reported. When patients are on high doses of basal insulin, such as with this patient, we are especially mindful to identify hypoglycemia. Other considerations in this patient include maximizing metformin use based on EGFR intolerance, and if there are no contraindications, the weight-promoting sulfonylurea and TZD may be replaced with a medication associated with weight loss, such as a GLP-1 receptor agonist or dual-GIP GLP-1 receptor agonist. If there are no contraindications, an SGLT2 inhibitor may also be added if needed. As discussed in regards to our patient case, for patients using insulin, assessing for overbasalization is essential. Clinicians should be alerted to this when basal insulin doses exceed 0.5 units per kilogram per day. Hypo- and hyperglycemia may be apparent, but hypoglycemia unawareness is also a possibility. If patients frequently need to correct the hypoglycemia, overall caloric consumption increases, which contributes to weight gain. Diabetes glucose monitoring should be offered for diabetes management in adults with diabetes on basal insulin. This provides useful information for safe insulin titration, as well as pattern recognition for patients. Pharmacotherapy is recommended as an adjunct to nutrition, physical activity, and behavioral counseling for individuals with type 2 diabetes and BMI of 27 or greater, and 25 or greater in Asian populations. The field of obesity medicine is exciting as new medications are being added to the market often. There are medications in the pipeline not yet approved specifically for weight loss, but we know that there will be more in the near future. This provides a brief list of the medications currently FDA approved for weight loss. We will review these medications in further detail on subsequent slides. When selecting an anti-obesity medication, or AOM, it's all about balance. We want to identify indications and contraindications to pharmacotherapy. Of course, the patient as a whole needs to be considered, including their comorbid conditions. We want to individualize care. Phentermine, which was approved in 1959, is the oldest anti-obesity medication on the market. Noradrenergic activation leads to appetite suppression. It is a controlled substance and is only approved for short-term use. It is safe to use in patients with type 2 diabetes, but caution should be exercised in individuals with cardiovascular disease. Adverse effects include elevated blood pressure and tachycardia. Orlistat was approved in 1999. It is a gastric lipase inhibitor that, when taken three times a day with meals, leads to fecal excretion of fat. Potential side effects include abdominal discomfort, oily stools, and flatulence. Caution should be exercised when taking medications that have a narrow therapeutic index, as medication malabsorption can occur. Similarly, malabsorption can occur with fat-soluble vitamins. Orlistat is safe and effective to use with metformin. When compared to placebo, orlistat-treated patients had a statistically significant weight reduction and improvement in fasting glucose. The combination of fentermine to pyrimate was approved in 2012. Like fentermine, it is a controlled substance. Unlike fentermine alone, the combination of fentermine to pyrimate is approved for long-term use. When compared to placebo, fentermine to pyrimate-treated patients experienced statistically significant improvements in percent change in body weight and percentage of patients achieving greater than or equal to 5% weight loss. Between-group differences were also significant, with greater improvements seen at the maximum dose, which is 15 mg of fentermine and 92 mg of dipyrimate. Dose-related trends were noted for rates of dry mouth, constipation, dyskusia, parasitias, insomnia, dizziness, anxiety, irritability, and disturbance in attention. Naltrexone bupropion was approved in 2014. Bupropion is a dopamine norepinephrine reuptake inhibitor that stimulates POMC neurons to release alpha-melanocyte-stimulating hormone, which ultimately leads to decreased hunger. Naltrexone is an opioid receptor agonist. Its action augments POMC firing. When compared to placebo, there was a statistically significant reduction in body weight and hemoglobin A1c at 56 weeks with naltrexone bupropion. I will use the next few slides to review GLP-1 receptor agonist, as medications in this class are approved for diabetes and weight loss individually. GLP-1 is produced by L-cells in the intestine and is degraded by DPP-4. It acts to delay gastric emptying, increase beta-cell insulin secretion, and increase satiety through the hypothalamus. Notable adverse effects include nausea, vomiting, and constipation. GLP-1 receptor agonists are contraindicated in patients with a history of pancreatitis, a personal or family history of multiple endocrine neoplasia type 2, and medullary thyroid cancer. Laraglitide and somaglitide are in the class of GLP-1 receptor agonists. Laraglitide was approved in 2010 for the treatment of type 2 diabetes and in 2014 for weight management. It is a daily injection. For diabetes, the maximum approved dose is 1.8 milligrams, and for weight management, the maximum approved dose is 3 milligrams daily. The scale diabetes randomized control trial examined the efficacy of laraglitide for weight loss among patients with type 2 diabetes. Results showed a statistically significant reduction in systolic blood pressure, mean waist circumference, body mass index, and hemoglobin A1c in the laraglitide group. The 3 milligram dose of laraglitide produced more weight loss and a statistically significant reduction in waist circumference, body mass index, hemoglobin A1c, and fasting plasma glucose when compared to the 1.8 milligram dose. Somaglitide, similar to laraglitide, is approved for both type 2 diabetes and weight management, with FDA approvals occurring in 2017 and 2021, respectively. It is a weekly injection titrated up to 2 milligrams for diabetes and 2.4 milligrams for weight management. However, only the maximally tolerated dose is recommended as we individualize care for patients. The STEP trials examined the somaglitide 2.4 milligram dose compared to placebo. At 68 weeks, mean change in weight was 14.9 percent in the somaglitide group compared to 2.4 percent with placebo. Importantly, we also learned that stopping somaglitide following a 20-week run-in period and switching to placebo resulted in weight regain, whereas those that continued on somaglitide experienced further weight loss. Terzapotide is a dual-glucose-dependent, insulinotropic, polypeptide, and glucagon-like peptide receptor agonist. GLP-1 slows gastric emptying, increases beta cell insulin secretion, and increases satiety. GIP is produced by K-cells in the intestine in response to glucose. It promotes insulin release from the pancreas. Terzapotide was approved for the treatment of type 2 diabetes in May 2022. It is a once-weekly injection. The Surmount Double Blind Randomized Placebo Control Trial examined terzapotide for weight management in people living with obesity and type 2 diabetes. There was a statistically significant reduction in hemoglobin A1c and waist circumference for the 10 and 15 milligram doses when compared with placebo. The SURPASS trial compared the efficacy of terzapotide to somaglitide 1 milligram in people with type 2 diabetes treated with metformin. Terzapotide was superior to somaglitide with respect to mean change in hemoglobin A1c and at all doses was superior in weight loss. In summary, when treating a patient with type 2 diabetes and obesity, one must treat both conditions. Weight loss leads to improved glycemia and often improves insulin resistance, which can sometimes result in diabetes remission. When appropriate, anti-obesity medications should be added as they are safe and effective in people with type 2 diabetes. In patients with overweight and obesity, weight-neutral medications or medications that promote weight loss are the preference. Of course, treatment must be in line with the guidelines of the CDC. Of course, treatment must be individualized to the patient, taking other medical conditions into consideration. Thus, coordinating care across specialties is essential when caring for these complex patients.

comprehensive care plan

diabetes

obesity

medications

glycemic control