Semaglutide, tirzepatide, and dulaglutide achieve similar results and have similar mechanisms of action, so the choice often comes down to preference and tolerability.
Glucagon-like peptide-1 receptor agonists (GLP-1) medications are used to treat patients with type 2 diabetes and obesity. GLP-1 medications such as semaglutide, tirzepatide, and dulaglutide help control blood glucose and appetite. The newest of the three is tirzepatide, approved by the FDA in 2023. Its notable difference is that it works on both GLP-1 and glucose dependent insulinotropic polypeptide receptors (GIP).1,2
Research shows that semaglutide, tirzepatide, and dulaglutide are each efficacious in lowering HbA1c and body weight1, and the newer once-weekly injectable tirzepatide has shown similar weight loss results as semaglutide.1 The SOURMOUNT-1 trial, however, found that reduction in baseline weight of 15 percent, 19.5 percent, and 20 percent at 72 weeks with the 5mg, 10mg, and 15mg doses of tirzepatide surpassed the performance of semaglutide3; it’s also reported that tirzepatide resulted in greater weight loss than dulaglutide1, which is good news for patients because of its recent FDA approval for weight loss.4
Because semaglutide, tirzepatide, and dulaglutide produce similar results in the context of type 2 diabetes and weight loss, the choice regarding which medication to prescribe comes down to preference, patient tolerance, cost, administration (oral or injectable), and patient responsiveness. Below is a general overview of each medication.
| Medication | Brand Name | Who? |
| Semaglutide (oral and injectable)
| Ozempic® Wegovy® Rybelsus®
| Adults with poor glycemic control and/or those taking more than one oral antihyperglycemic agent (e.g., metformin); patients with obesity (BMI ³ 30 kg/m2); insulin patients who need more intense treatment; renal or hepatic impairment; patients at risk for CVD or established CVD.5,6,7
|
| Tirzepatide
| Mounjaro® Zepbound® | Adults with type 2 diabetes or obesity |
| Dulaglutide
| Trulicity® | Adults with type 2 diabetes and obesity, and children 10 or older with type 2 diabetes; patients who have not responded to oral medications. |
| Medication | Brand Name | What? |
| Semaglutide | Ozempic Wegovy Rybelsus
| Semaglutide works via the incretin hormone system. As a synthetic form of the hormone glucagon-like peptide (GLP-1), semaglutide is released from the proglucagon gene found in the L-cells of the small distal intestine and colon. GLP-1 binds itself to GLP-1 receptors in pancreatic beta cell, gastric mucosa, kidney, heart, and hypothalamus tissue, where it stimulates the release of insulin in hyperglycemic sates and inhibits glucagon release in hyperglycemic states. It also slows gastric emptying and suppress one’s appetite.1
Adjunct therapy to diet and exercise.
|
| Tirzepatide
| Mounjaro Zepbound | Dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist; it mimics naturally occurring GLP-1 and GLP-1 hormones, reduces appetite, and slows stomach emptying.
Adjunct therapy to diet and exercise.
|
| Dulaglutide
| Trulicity | Mimics naturally occurring GLP-1 and GLP-1 hormones, reduces appetite, and slows stomach emptying. Dulaglutide stimulates insulin secretion after meals and reduces the amount of glucose produced by the liver.8
Adjunct therapy to diet and exercise. |
| Medication | Brand Name | When? |
| Semaglutide | Ozempic
| Once weekly subcutaneous single dose pre-filled pen
|
| Wegovy
| Once weekly subcutaneous single dose pre-filled pen
| |
| Rybelsus
| Once daily oral tablet taken with water 30 minutes before eating
| |
| Tirzepatide
| Mounjaro Zepbound | Once weekly subcutaneous single dose pre-filled pen
|
| Dulaglutide
| Trulicity | Once weekly subcutaneous single dose pre-filled pen |
| Medication | Brand Name | How? |
| Semaglutide
| Ozempic
| 0.25mg, 0.5mg, 1.0mg, 2.0mg.
During week five (5), the dose increases to 0.5mg; for adults with type 2 diabetes, the dosage could increase to the maximum 2.0mg for better glycemic control.
|
| Wegovy
| 0.25mg, 0.5mg, 1.0mg, 1.7mg, 2.4mg
Dosing begins with 0.25mg for four (4) weeks and increase every four (4) weeks until the maximum dose, not to exceed 2.4mg, is determined by the treating physician.
| |
| Rybelsus
| 7mg or 14mg | |
| Tirzepatide
| Mounjaro Zepbound | 2.5mg, 5mg, 7.5mg, 10mg, 12.5mg, 15mg
Must be refrigerated.
|
| Dulaglutide
| Trulicity | 0.5mL, 0.75mL, 1.5mg, 3.0mg, 4.5mg
Adult recommended starting dose: 0.75mg with 1.5mg weekly increases after at least four (4) weeks on the current dose if more glycemic control is needed. Do not exceed the maximum dose of 4.5mg.
Pediatric recommended starting dose: 0.75mg. If more glycemic control is needed, increase to the maximum dose of 1.5mg after at least four (4) weeks on the 0.75mg dose. Do not exceed 1.5mg.
Must be refrigerated.
|
| Medication | Brand Name | Why? |
| Semaglutide | Ozempic Wegovy Rybelsus
| Lower risk of death caused by metabolic syndrome and health complications caused by type 2 diabetes.
|
| Tirzepatide
| Mounjaro Zepbound | Lower risk of death caused by metabolic syndrome and health complications caused by type 2 diabetes; to date no FDA indication for reducing CV2. |
| Dulaglutide
| Trulicity | Lower risk of death caused by metabolic syndrome and health complications caused by type 2 diabetes. |
Implications for Clinical Practice: GLP-1s as Adjuncts to Diet and Exercise
Commonly reported side effects of GLP-1 medications include gastrointestinal events such as bloating, nausea, vomiting, and diarrhea.9,10,11 To offset the side effects and to ensure nutritionally needs are being met, supplementing patients’ diets with nutritionally designed meal replacements for patients prescribed GLP-1 medications warrants consideration. Supplementing patients’ diets with nutritionally designed meal replacements can help patients ensure they are consuming the RDA for vitamins, minerals, protein, and fiber while also helping them manage the GI side effects of GLP-1 medications.
In addition to the GI side effects, patients can lose muscle mass quickly when food consumption is reduced. Loss of mean muscle mass can adversely affect major organs of the body; most importantly, muscle is metabolically active, requiring energy to sustain itself. When one has more lean mass, their resting metabolic rate is increased, which translates into an increase in the number of calories being burned. In short, more lean mass results in higher energy expenditure because of the increased metabolic rate.
To ensure nutritional needs are being met, pre-packaged, nutritionally designed shakes/beverages offer convenience and satisfy daily recommendations for vitamins and minerals. Nutritionally designed shakes/beverages have the added benefit of reducing GI side effects and should be considered as part of patients eating healthy plan while on weight loss medications.
Sources:
1 Use of dulaglutide, semaglutide, and tirzepatide in diabetes and weight management
2 Model-based simulation of glycemic effect and body weight loss when switching from semaglutide or dulaglutide to once weekly tirzepatide
3 Tirzepatide once weekly for the treatment of obesity
4 FDA approves diabetes drug tirzepatide for chronic weight management
5 Integrating oral semaglutide into clinical practice: For whom, when, and how?
6 Pharmacological profile of once-weekly injectable semaglutide for chronic weight management
7 Semaglutide for the treatment of obesity
8 Dulaglutide: An evidence-based review of its potential in the treatment of type 2 diabetes
9 Gastrointestinal tolerability of once‐weekly Semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss
10 Efficacy and tolerability of tirzepatide, a dual glucose- dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes: A 12-week, randomized, double-blind, placebo-controlled study to evaluate different d
11 Efficacy and safety profile of once-weekly dulaglutide in type 2 diabetes: A report on the emerging data
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