Are GLP-1's miracle drugs for broad cardio-metabolic improvements?

GLP-1's, whether approved for treating T2 diabetes or obesity, seem to have interesting additional health benefits, such as improvement in sleep (apnea), encouraging cardiovascular (CVD) risk data and more.

Are these miracle drugs with unexplainably broad cardio-metabolic effects or, as some say, "it's all about the weight loss" that is then resulting in improvements in CVD outcomes.

To address this question, we decided to compare published outcomes between the Virta Treatment and these GLP-1 drugs.

For context, we at Virta Health use nutrition to improve metabolic health and reverse T2 diabetes (T2D). While we mostly talk about T2D reversal and weight loss, our published and peer-reviewed outcomes demonstrate very broad metabolic health improvements.

In fact, when you look at the table below, Virta delivers the same or better cardio-metabolic health outcomes nutritionally, as compared to GLP-1's. (without the costs, risks and side-effects associated with the drugs).

Weight loss or some other direct impact?

Interestingly, we at Virta Health have faced the same question: "Nothing special here, your patients lose amazing -13% of body weight, so all the 'ancillary benefits' like diabetes reversal, inflammation, depression, kidney, liver... improvements are simply due to the weight loss. Or can you prove otherwise?"

Well, there are at least two answers to this question:

1. Does it matter? When we deliver broad cardio-metabolic improvements across 10+ biomarkers / co-morbidities, isn't that enough? Do we even need to know the mechanism today?
2. Some evidence... we do know from our published and internal data that our patients see remarkable improvements (even full T2D reversal) before substantial weight loss occurs. This doesn't necessarily prove that our (or GLP-1's) broad cardio-metabolic improvements happen independent of weight loss.

Net net, whether GLP-1's are miracle drugs or not, we know for sure that we can deliver the same or better broad cardio-metabolic improvements with nutrition alone. What we can't yet say with confidence is whether those improvements are "only because of weight loss" or some other mechanism, but in day to day patient care improving lives and saving money for the healthcare industry, it doesn't really matter.

We'll have answers to all questions in due time though...

Back to reversing T2 diabetes and delivering broad cardio-metabolic outcomes!

REFERENCES:

1. Hallberg SJ, McKenzie AL, Williams PT, Bhanpuri NH, Peters AL, Campbell WW, et al. Effectiveness and safety of a novel care model for the management of type 2 diabetes at 1 year: an open-label, non-randomized, controlled study. Diabetes Ther. 2018;9(2):583-612..
2. Athinarayanan SJ, Adams RN, Hallberg SJ, McKenzie AL, Bhanpuri NH, Campbell WW, et al. Long-term effects of a novel continuous remote care intervention including nutritional ketosis for the management of type 2 diabetes: a 2-year non-randomized clinical trial. Front Endocrinol (Lausanne). 2019;10:348.
3. Athinarayanan SJ, Vantieghem M, McKenzie AL, Hallberg S, Roberts CG, Volk BM, et al. 832-P: Five-year weight and glycemic outcomes following a very-low-carbohydrate intervention including nutritional ketosis in patients with type 2 diabetes. Diabetes. 2022;71(Suppl 1).
4. Athinarayanan SJ, Hallberg SJ, McKenzie AL, Lechner K, King S, McCarter JP, et al. Impact of a 2-year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes. Cardiovasc Diabetol. 2020;19:1-13.
5. Vilar-Gomez, E., Athinarayanan, S. J., Adams, R. N., Hallberg, S. J., Bhanpuri, N. H., McKenzie, A. L., ... & Chalasani, N. (2019). Post hoc analyses of surrogate markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in patients with type 2 diabetes in a digitally supported continuous care intervention: an open-label, non-randomised controlled study. BMJ open, 9(2), e023597.
6. Athinarayanan SJ, Roberts CGP, Adams RN, Volk BM, Phinney SD, Volek J, McKenzie AL. Two-Year (2y) eGFR Slope in People with Type 2 Diabetes (T2D) Receiving a Very Low Carbohydrate Diet (VLCD) Intervention. Diabetes. 2023;72(Suppl 1):410-P. doi:10.2337/db23-410-P.
7. Adams RN, Athinarayanan SJ, McKenzie AL, Hallberg SJ, McCarter JP, Phinney SD, Gonzalez JS. Depressive symptoms improve over 2 years of type 2 diabetes treatment via a digital continuous remote care intervention focused on carbohydrate restriction. J Behav Med. 2022;45(3):416-427.
8. Siegmann MJ, Athinarayanan SJ, Hallberg SJ, McKenzie AL, Bhanpuri NH, Campbell WW, et al. Improvement in patient-reported sleep in type 2 diabetes and prediabetes participants receiving a continuous care intervention with nutritional ketosis. Sleep Med. 2019;55:92-99.
9. Lyman KS, Athinarayanan SJ, McKenzie AL, Pearson CL, Adams RN, Hallberg SJ, et al. Continuous care intervention with carbohydrate restriction improves physical function of the knees among patients with type 2 diabetes: a non-randomized study. BMC Musculoskelet Disord. 2022;23(1):297.
10. Phinney S, Adams R, Athinarayanan S, McKenzie A, Volek J. SAT-LB125 Broad spectrum effects of a ketogenic diet delivered by remote continuous care on inflammation and immune modulators in type 2 diabetes and prediabetes. J Endocr Soc. 2020;4(Suppl 1):SAT-LB125.
11. Li Z, Zhang Y, Quan X, Yang Z, Zeng X, Ji L, et al. Efficacy and acceptability of glycemic control of glucagon-like peptide-1 receptor agonists among type 2 diabetes: a systematic review and network meta-analysis. PLoS One. 2016;11(5):e0154206.
12. Kosiborod MN, Bhatta M, Davies M, Deanfield JE, Garvey WT, Khalid U, et al. Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses. Diabetes Obes Metab. 2023;25(2):468-478.
13. Aronne LJ, Sattar N, Horn DB, Bays HE, Wharton S, Lin WY, et al; SURMOUNT-4 Investigators. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA. 2024;331(1):38-48.
14. Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J, et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 2021;398(10313):1811-1824.
15. Sheahan KH, Wahlberg EA, Gilbert MP. An overview of GLP-1 agonists and recent cardiovascular outcomes trials. Postgrad Med J. 2020;96(1133):156-161.
16. Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384(12):1113-1124.
17. https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=167028?
18. https://investor.lilly.com/news-releases/news-release-details/tirzepatide-reduced-sleep-apnea-severity-nearly-two-thirds
19. https://www.medscape.com/viewarticle/semaglutide-improves-knee-osteoarthritis-pain-physical-2024a10007s0?form=fpf
20. Wilson JM, Lin Y, Considine G, Cox AL, Bowsman LM, Robins DA, et al. The dual GIP/GLP-1 receptor agonist tirzepatide improves cardiovascular risk protein biomarkers in patients with type 2 diabetes. Circulation. 2020;142(Suppl 3):A13426.