Oral Peri-operative TIming of Metformin (or) Salsalate to Improve Non-cardiac Surgery Glucose Control

Summary

Hypothesis: In surgical patients with type 2 diabetes, taking either metformin or salsalate on the morning of surgery will reduce the incidence of hyperglycemia, inflammation and even surgical site infections, without any obvious patient risk relative to patients given a placebo control. Anesthesia and surgery induce a number of metabolic disturbances, particularly among patients with type 2 diabetes (T2D). This includes altered glucose metabolism and hyperglycemia, which is associated with significant morbidity and mortality, including an increase in surgical site infections (SSI). Although insulin protocols can reduce blood glucose levels in hyperglycemic surgical patients, leading to reduced SSI, this has caused severe hypoglycemia in a number of patients. Instead, the use of simple and effective interventions, such as continuing metformin on the day of surgery, could represent an important step toward reducing the incidence of these morbid outcomes while improving glucose control. Alternatively, salsalate, a non-acetylated dimer of salicylic acid, has also emerged as a novel glucose-lowering medication that also possesses important anti-pyretic and anti-inflammatory properties and could prove equally effective.These refinements may also reduce SSI and inflammation. If the proposed pilot trial, to continue metformin, or take salsalate, peri-operatively, is as safe and easy as the investigators anticipate it will allow for the planning of a future definitive randomized clinical trial. The aims of this pilot trial are to assess the feasibility of safely continuing metformin, or taking salsalate on the day of surgery, with the goal of reducing the incidence of hyperglycemic events. This includes assessing our ability to recruit patients, adhere to the proposed study protocol, assess workload,and measure the desired outcomes, all of which are crucial for the planning of a subsequent clinical trial.

Timeline

Start

2023-12-01

Primary completion

2024-06-01

Completion

2024-12-01

Publications

• Background Palermo NE, Gianchandani RY, McDonnell ME, Alexanian SM. Stress Hyperglycemia During Surgery and Anesthesia: Pathogenesis and Clinical Implications. Curr Diab Rep. 2016 Mar;16(3):33. doi: 10.1007/s11892-016-0721-y.
• Background Frisch A, Chandra P, Smiley D, Peng L, Rizzo M, Gatcliffe C, Hudson M, Mendoza J, Johnson R, Lin E, Umpierrez GE. Prevalence and clinical outcome of hyperglycemia in the perioperative period in noncardiac surgery. Diabetes Care. 2010 Aug;33(8):1783-8. doi: 10.2337/dc10-0304. Epub 2010 Apr 30.
• Background Membership of the Working Party; Barker P, Creasey PE, Dhatariya K, Levy N, Lipp A, Nathanson MH, Penfold N, Watson B, Woodcock T. Peri-operative management of the surgical patient with diabetes 2015: Association of Anaesthetists of Great Britain and Ireland. Anaesthesia. 2015 Dec;70(12):1427-40. doi: 10.1111/anae.13233. Epub 2015 Sep 29.
• Background Smith BK, Ford RJ, Desjardins EM, Green AE, Hughes MC, Houde VP, Day EA, Marcinko K, Crane JD, Mottillo EP, Perry CG, Kemp BE, Tarnopolsky MA, Steinberg GR. Salsalate (Salicylate) Uncouples Mitochondria, Improves Glucose Homeostasis, and Reduces Liver Lipids Independent of AMPK-beta1. Diabetes. 2016 Nov;65(11):3352-3361. doi: 10.2337/db16-0564. Epub 2016 Aug 23.

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