Pre-Diabetes and T2DM Treatment
Starting and advancing medication in pre-diabetes and T2DM is important to address the metabolic defects. We can now treat diabetes, not just chase blood sugars.(1) And data suggests combination therapy is more efficacious than step-wise therapy.(2) Landmark trials show aggressive management early in the diagnosis, helps prevent/delay complications decades later (the Legacy Effect). (DCCT and UKPDS)(3)
Metformin may not always be the initial medication therapy in T2DM or in pre-diabetes(3). However, more often than not, it is. Writing the eRX for Metformin XR 500mg helps reduce the GI issues. The 500 XR mg dose is typically priced the same as the IR (immediate release). Intensifying/titrating the dose weekly until the fasting glucose is less than 110mg or the clinical therapeutic dose is reached (1000mg bid), offers patients increased independence as well as trackable improvement when they are diagnosed.
Starting a suboptimal dose and then scheduling a 3-6 month follow-up is clearly clinical inertia. Don’t be guilty of that shameful label.
ADA 2020 – 2022 guidelines recommended initiating GLP1-RAs after metformin for patients as RISK of CVD, regardless of A1C.(3) Which of our T2DM patients are at risk of CVD? Do they have a heart? And is it beating? If they have T2DM they are very likely at risk for CVD. Our T2 patients are 2-4 times more likely to be at risk for CVD, and that risk begins with PRE-DIABETES.4,5 Pre-diabetes may be present 7-10 years before the diagnosis of full-blown diabetes.
Guidelines are now matching research, not lagging behind by years and years.(3) So, we have the power of research to drive practice. That will be helpful if you have reluctant insurance companies and need to do prior auths.
GLP1-RAs with proven benefit (FDA indication for CV risk reduction) are Dulaglitide (Trulicity), Semaglutide (Ozempic) and Liraglutide (Victoza). Surely one of these is on the patient’s formulary.
Gut- Liver – Pancreas
When explaining this class to my patients, I use the analogy of a Thermostat. These meds kick in to help get insulin out of the pancreas when you need it, after you eat. And then they shut off when you don’t need them. How do they do that? If I said Glucagon-Like-Peptide: glucose dependent insulin release and reduction in hepatic glucose release, eyes would roll. GLP: Gut – Liver – Pancreas. They help food enter the gut at a more normal speed. They help the liver calm down and not make so much sugar. And they help get the insulin out when it’s needed. AND the bonus—They speak to the brain and say “you are full – – You are NOT hungry”. So weight loss may happen. 6-8-10, even 12 lbs with the higher doses. A1C reduction of ~1-2% is expected.
When initiating these non-insulin injections, start with the lowest dose, even lower than the manufacturers recommended titration to reduce or mitigate GI adverse events. Coach the patient that they may experience some “queasiness” the first few weeks, but it should go down to little of nothing. And then ask “if that happens, can you power through it?” You want a verbal commitment for your patient to stick with it and not bail out at the first sign of problems. Reduce fatty/spicy foods for a while. Stop eating when you are full. Or, snack for the first few days. I never say “nausea, vomiting, barf bag…..” I don’t want any self-fulfilling prophesy.
Another class of diabetes meds with significant research for cardiac, heart failure treatment and renal protection are the SGLT2’s.3 These pills focus on the kidneys, blocking the path (in the distal tubules) so the glucose is not re-circulated, but rather pushed out in the urine. This loss of glucose (calories), sodium, and fluid, helps with glucose control, blood pressure, and weight loss. Empagliflozin (Jardiance), Canagliflozin (Invokana), Dapagliflozin (Farxiga) and Ertugliflozin (Steglatro) are the drugs in this class. They have demonstrated cardiac risk reduction, with Farxiga and Jardiance being approved for HF, independent of diabetes. Invokana has a renal indication with significant slowing of GFR decline. Other agents renal studies are near completion.
Patient coaching must include increasing fluid intake, using good hygiene to prevent risk of UTI and GMI.
These medications should be top considerations for patients with T2DM as they offer much more than glycemic benefit.
AND they can be used together. This may reduce or delay the need for insulin.
- DeFronzo RA. Diabetes. 2009;58(4);772-795.
- Peng XV, Ayyagari R, Lubwama R, et al. Impact of Simultaneous Versus Sequential Initiation of Basal Insulin and Glucagon-like Peptide-1 Receptor Agonists on HbA1c in Type 2 Diabetes: A Retrospective Observational Study. Diabetes Ther, Feb 2020.
- American Diabetes Association. Standards of Medical Care in Diabetes-2022. Diabetes Care January 2022, 44(supplement 1).
- The Emerging Risk Factor Collaboration. Lancet.2010;375(9733);2215-2222.
- Laaskso M. Diabetes Care 2010; 33(2);442-449.