Just some highlights to remember
50% of world population is thought to be obesity and thought to be a master switch for a variety of disorders such as diabetes, cardiovascular disease, liver disease and kidney.
30-40% of Diabetics develop chronic kidney diseases and presence of albuminuria raises risk.
38% of adults have MASH with very low diagnosis rates of which nearly 10% may proceed to cirrhosis.
Wegovy (semaglutide) approval came from MASH F2-F3 in Aug 2025. Ozempic approved for CKD for risk reduction in Jan 2025. Zepbound (Tirzepatide) was the first pharmacotherapy approved for sleep apnea reduction ( about 40 events/hr) in people with obesity and can cause nearly 20.9% weight reduction (SURMOUNT-1, 72 weeks). These are all once weekly doses.
FLOW trial changed the CKD field – In idabetes, it used to be metformin for lowering HbA1c with last step for Insulin. FLOW redefined CKD as GLP1 indication and preserving kidneys saving nearly $90K dialysis costs per yeear.
MASH – now have two treatment paradigms – Rezidffra (Liver targeted for fibrosis centric disease) and Wegovy (for systemic metabolic disease)
The diabetes field has moved beyond GLP1 monotherapy to combination with Amylin: such as Petrelintide + CT388 which combine dual GLP1 with Amylin.
The MASH field has moved to FGF21 analogs such as Pegozafermin from 89bio.
The T2D foundation has moved to market maturation with combination therapy.
The oral semaglutide has shown almost a 13% reduction in weight with once a day oral dosing, though it is not indicated for reduction of MASH. It is affordable at $149 per month compared to the prcie of $199 per month for the injectable.
Orforglpron is an oral for chronic weight management is also in studies and causes ~12% weight loss. Interestingly similarly to oral semaglutide, it is a normal distribution with some people losing more weight than others. It is about $149 per month but may go to $399 per month and may be behind oral semaglutide in algorithm.
The triple inhibitor Retatrutide has multiple studies ongoing for multiple indications and has enormous weight loss – some clinical trial participants left because they felt it would be too much weight loss!
A related condition called Lp(a) excess that is important for Cardiovascular. Lp(a) can vary between individuals and not correlated with LDL-C levels. It is a genetic condition and cannot be controlled through diet or something else. Pelacarsen is for CVD reduction through oligonucleotide based regulation of Lp(a) and showed a reduction in Lp(a) of nearly 80% in patients.
