EVERYONE WANTS THEIR GLP-1 TO BE THE ONE

The two big players in the GLP-1 market are the Danish pharmaceutical company Novo Nordisk, and Indiana-based Eli Lilly and Co. Novo Nordisk has put its money on semaglutide which has been marketed as Ozempic, Wegovy, and Rebelsus, and Lilly has run with tirzepatide. Semaglutide is a weekly injection and is known more as Ozempic because of the catchy “O-O-Ozempic” tune. Semaglutide also comes in tablet form and is sold as Wegovy and Rebelsus. Recently, Rebelsus oral preparation changed its name to Ozempic oral.

Tirzepatide is Lilly’s Zepbound and Mounjaro, and both are administered as a once weekly subcutaneous injection. An FDA-approved oral preparation of tirzepatide does not exist…yet. Lilly’s oral GLP-1 is a completely different drug known generically as orforglipron and commercially as Foundayo. Articles comparing all of these very popular drugs are published often in scientific journals. 

A few of those comparison studies are mentioned in the information that follows:

1.  Eli Lilly did a head-to-head comparison of oral Foundayo to Novo Nordisk’s oral Ozempic in the treatment of type 2 diabetes and obesity. Foundayo achieved larger reductions in A1C and greater weight loss compared to oral Ozempic.  
2. Lilly also did a head-to-head comparison of injectable tirzepatide, Zepbound, and oral Foundayo for weight loss and learned that the injectable GLP-1 resulted in greater weight loss than oral Foundayo, but by only a few percentage points.
3. Lilly compared Foundayo to once-daily insulin glargine (Lantus) for cardiovascular outcomes in patients with type 2 diabetes. Cardiovascular outcomes are non-fatal heart attack, non-fatal stroke, cardiovascular death, and hospitalization for unstable angina (chest pain). After two years on one or the other treatment, a CV outcome occurred in 4.2% of Foundayo and 5.0% of glargine patients—nearly the same. In type 2 diabetics, Foundayo lowered A1C levels better than glargine insulin, and generated a significantly greater weight loss than glargine. In regard to total major adverse cardiovascular events, Foundayo and glargine insulin were nearly identical—16.2% (Foun) vs. 18.8% (glarg). Of the 2749 patients studied, 62 died—43 patients on glargine, 19 patients on Foundayo, or 2 and a half times as many deaths in insulin glargine. Hypoglycemia was three times more common with insulin glargine patients than tirzepatide.
4. Lilly studied Foundayo and compared it to oral Ozempic. Foundayo “offers greater weight loss and better blood sugar control than a higher dose of Ozempic oral in adults with type 2 diabetes.” It also produced larger reductions in A1C levels in type 2 diabetics. 
5. Novo Nordisk published a study comparing injectable and oral semaglutide to one another but also to five other GLP-1’s and insulin glargine in type 2 diabetics. Subq semaglutide reduced A1C by 1.8% while oral semaglutide reduced A1C by 1.4%. Both preparations of semaglutide were superior to insulin glargine and five other GLP-1’s in lowering A1C. Subq semaglutide reduced body weight significantly more than all comparators tested except tirzepatide. Oral semaglutide reduced body weight more than sitagliptin and liraglutide, but not better than tirzepatide. 
6. Eli Lilly compared 4 strengths of their oral GLP-1, orforglipron, to placebo after 26 weeks and 36 weeks. Weight loss was between -8.6% to -12.6% for orforglipron and -2.0% for placebo. At week 36, orforglipron achieved between -9.4% to -14.7% weight loss compared to -2.3% with placebo. 

All of the above studies are designed to show superiority of one drug, or dosage form, over another or over placebo. What shakes out amid all the confusion and options are the following conclusions:

   GLP-1’s are superior to placebo in controlling blood sugar, reducing A1C, and reducing

     weight

   Subq administration of GLP-1’s produces lower A1C, blood sugar, and weight loss levels

      than oral forms of GLP-1’s

   GLP-1’s are superior to insulin glargine in controlling blood sugar and A1C levels

   Tirzepatide is superior to all other GLP-1’s and insulin glargine in improving the parameters 

      mentioned previously

This is a good summary of the efficacy of GLP-1’s. I hope it’s not so medically esoteric that it was difficult to understand. These are drugs that have significant, and very useful indications that are practical and meaningful for obese patients or diabetics.

References: Del Prato S, Kahn SE, et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk: a randomized, open-label, parallel-group, multi center, phase 3 trial. The Lancet 2021 Nov 13; 398(10313):1811-1824.  

Meier JJ. Efficacy of Semaglutide in a subcutaneous and oral formulation. Front Endocrinol 2021 June 25;12:645617.

Tucker M. Orforglipron Noninferior to Insulin Glargine for Cardiovascular Outcomes in Type 2 Diabetes. medscape.com 2026 October 1.

medscape.com Lilly Touts Foundayo Advantage Over Novo’s Ozempic Pill in Diabetes Analysis 2026 September 29.

Wharton S., Blevins T., et al. Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. N Engl J Med 2023 Sept 7;389(10):877-888. 

Gallwitz B., Giorgino F. Clinical Perspectives on the Use of Subcutaneous and Oral Formulations of Semaglutide Front Endocrinology 2021 Jun 29;12:645507.