Orforglipron: The next big thing?

[druell235]

Have any of the studies covered how Orforglipron interacts with metformin. I am still on metformin and don't want to quit when I start researching this.

 

[Calm Logic]

I doubt there are such studies yet, but it should be fine.

Obesity specialists have been adding metformin occasionally for some people already on a GLP, like when someone on sema or tirz wants a boost but can't raise the dose yet due to the dosing schedule.

 

[Calm Logic]

By the way, brand-name Jardiance is available from India.

Personally, I don't see the need for having Jardiance or metformin along with a GLP, since a GLP is much stronger. (My internist wanted me to increase the dose for tirz even weekly, if necessary.)

OTOH, metformin increases the body's natural production of GLP-1. So it may be good while on a strict dosing schedule. Like people tend to feel hungrier on day five of a weekly dose of tirz.

 

[byefatlicia]

By the way, brand-name Jardiance is available from India. But I personally don't see the need for having Jardiance or metformin along with a GLP, since a GLP is much stronger.

Have you seen anything on skyrizy?

 

[Calm Logic]

Have you seen anything on skyrizy?

Not really. The one reputuble-looking seller on IndiaMart sells it for over $1,000 USD, which is still cheap compared to the price at GoodRx. And according to Google Gemini, it is still under a patent in India.

 

[byefatlicia]

Not really. The one reputuble-looking seller on IndiaMart sells it for over $1,000.

Okay thanks🙂 the brand name goes for 19k :0

 

[Calm Logic]

Yeah, I just noticed that and included the link to GoodRx. Insane.

 

[Calm Logic]

Have any of the studies covered how Orforglipron interacts with metformin. I am still on metformin and don't want to quit when I start researching this.

From an article on polypharmacy:

Why Do GLP-1 Drugs Stop Working, and What to Do About It?

Everybody has a set point, and every weight loss intervention eventually leads to a plateau, so it helps to have a variety of tools to support patients.

www.medscape.com

"You don't see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They're on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They're usually on three, four, five drugs, similar to what we would see with resistant hypertension."

 

[Calm Logic]

Source

 

[Habibibi]

View attachment 11105

Source

This is only true if 10% weight loss is considered "considerable " efficacy, I guess

 

[Calm Logic]

Yes, to get good efficacy, one would ideally switch from orfo to tirz (or reta) at some point. At 12 weeks, orfo is almost similar to tirz in effect. As time goes on, the average differences become painfully obvious, according to the studies. This is similar in idea to switching from sema to tirz.

 

[druell235]

From an article on polypharmacy:

Why Do GLP-1 Drugs Stop Working, and What to Do About It?

Everybody has a set point, and every weight loss intervention eventually leads to a plateau, so it helps to have a variety of tools to support patients.

www.medscape.com

"You don't see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They're on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They're usually on three, four, five drugs, similar to what we would see with resistant hypertension."

Thank you for sharing!!

 

[Calm Logic]

Gemini puts orfo in the same category as sema for effectiveness:

FINAL RANKING OF MEDICATIONS BY WEIGHT LOSS EFFECT (Highest to Lowest)

Rank	Medication(s)	Effectiveness Profile	Typical Weight Loss (1 Year)
1.	Setmelanotide (Imcivree)	Very High (Specific Genetic Use)	12.5% - 25.6% (Only for specific rare genetic conditions)
2.	Retatrutide (Investigational)	Very High / Investigational	17% - 24.2% of initial body weight
3.	Tirzepatide (Zepbound/Mounjaro)	Very High	15% - 22.5% of initial body weight
4.	Semaglutide (Wegovy/Ozempic)	High	10% - 15% of initial body weight
5.	Orforglipron (Investigational)	High (Oral)	9.2% - 12.4% of initial body weight
6.	Phentermine-Topiramate (Qsymia)	High/Moderate	7% - 11% of initial body weight
7.	Liraglutide (Saxenda)	Moderate	~8% of initial body weight
8.	Naltrexone/Bupropion (Contrave)	Moderate	5% - 10% of initial body weight
9.	Phentermine	Moderate (Short-Term Use)	3% - 10% of initial body weight
10.	Metformin & Jardiance (Combination)	Modest	3% - 6% of initial body weight[/b]
11.	Orlistat (Xenical/Alli)	Modest	~3% - 4% greater than diet alone
12.	Metformin	Modest	2% - 5% of initial body weight
13.	Jardiance (Empagliflozin)	Modest	2% - 3% of initial body weight
14.	Low-Dose Naltrexone (LDN)	Minimal/Variable	< 5% (Used alone, off-label)

SUMMARY OF DRUG CLASSES

• Very High Efficacy (Ranks 1-5): Primarily hormone agonists (GLP-1/GIP/Melanocortin system) that target the core biological mechanisms of appetite and metabolism.
  
• Moderate Efficacy (Ranks 6-9): Combination therapies and stimulants that use various mechanisms (appetite suppression, reward pathways) to achieve clinically significant, but generally lower, total weight loss.
  
• Modest Efficacy (Ranks 10-14): Older prescription drugs (Metformin, Jardiance) whose weight loss is a secondary effect, or fat-absorption blockers (Orlistat) and off-label single agents (LDN).