Are GLP-1s and SGLT2s replacements for Metformin or in addition to Metformin?

Dear Dr. Edelman, I’m confused about the SGLT2s and GLP-1 RAs. Are you supposed to take them with metformin, or are they a replacement for metformin?

Dr. Edelman: SGLT2 inhibitors (Farxiga, Invokana, Jardiance, Steglatro) and GLP1-RAs (Adlyxin, Byetta/Bydureon, Ozempic, Rybelsus, Trulicity, Victoza) have now become two of the most important classes of medications for type 2 diabetes. Both of these groups of medications have been shown to protect against heart disease and also progression of kidney dysfunction (primarily the SGLT2 inhibitors) that could lead to dialysis or transplantation.

Since the treatment algorithm put forth by the ADA says always start with metformin first, some professionals and people with diabetes are asking, why start with metformin and not with one or both of these two classes of medications?

Metformin has been around forever, it is generic and the cost is just pennies a day. It does have a good track record in terms of safety, and it does not lead to weight gain or hypoglycemia. Metformin is the first drug of choice around the world in every country, and you can add an SGLT2 or GLP1-RA to it if your HCP recommends it for you. However, starting with an SGLT2 inhibitor or a GLP-1 RA in an individual who is intolerant to metformin (primarily diarrhea) is a good choice, and even in the future we may see large diabetes organizations recommending these two classes as first line therapy once they get less expensive.

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    Would combining a SGLT-2 and a GLP-1 be a recommended in even a possible course of treatment? I have had major problems with metformin and intestinal problems so have been taken off of metformin.

  2. Dr. E: I have been taking Metformin for years of pumping. I have experimented with and without it and it saves me ~35% of my Insulin use with it. I have also done some experimenting on my own by varying the dosage to see the results. My normal dosage is 1000mg 2X and some of the results are interesting. I tolerate it very well. I am on a 670G using AUTO CGM totally resulting in a 6.4% A1c and over 90% in range continuously. My Carelink data is available at Medtronic for anyone to see. I am using the whole package more as a portion control system basing my control using the time honored 2 hour post prandial readings, and damned if it doesn’t work ! No one seems to be interested, which I have found previlent among TCOYD professionals, FYI. I have no way of acquiring the testing equipment necessary to see how much control/effect there is on Liver glucogon. I don’t consider the carb system a reasonable base reference anymore, and I am a healthy 65+ year T1D.

    • Rich…thanks for your comment, and congrats big time for TAKING CONTROL OF YOUR DIABETES. There have been several big studies looking at metformin in T1D, and they all showed no benefit though one did show about 10% lower insulin requirements. There are individual responses like yours which are very positive. Your TIR is totally awesome. See you at the next virtual ONE conference on Oct 3rd!

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      I am a person that do not like taking any medication however I was recently diagnosed with type 2 diabetes and immediately placed on Metformin.
      It upsets (diarrhea) my stomach terribly. I take it sometimes. I know this is not good.


      I’m looking for a more natural method for controlling my diabetes. I woul like a strict diet plan. Most plans just tell you to eat more veggies and whole grains. Can you list some foods for me? Now I just eat salads, turkey, chicken fish and nuts. Very seldom any breads. Need recipes for preparing different foods can u help me?

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    For a Type 1 LADA in honeymoon and not dependent on insulin, would using a GLT-1 or DDP-4 make sense to help preserve beta cell mass?

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    Newly t2d , on Metformin, numbers are good , a1c , 6.4, couldn’t take jardiance, keto, low carb diet, exercising, but no weight loss, today was started on ozempic once weekly. Not sure if I’m to take Metformin? Concerned about new side effects? On Metformin for five months, becoming overwhelmed with all the information and dos and donts. Doctors rush you and I forget to ask all my questions then I call and wait a day or two for a call back … can you tell me if Metformin can be taken with ozempic?

    • Metformin is taken with all the GLP1s including Ozempic, and is very common. Many people with type 2 (and many people without diabetes) have a tough time losing weight…good luck!

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      I take 2x metformin daily with Ozempic. I tried to quit metformin, but my glucose went up substantially, so for me, it makes a large difference. All my doctors have recommended both for best results.

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    My doc is talking adding ozempic. I could not tolerate victoza or trulicty in the past (they made me feel terrible). How likely is this to happen with ozempic?

    • Very likely. The stronger the drug, the more side effects. However, just like with Victoza, you can titrate slower with the pen than they suggest, and that almost always helps.

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