Type 2 Diabetes Remission and Substantial Body Weight Reduction Achieved with Metformin and a Sodium-Glucose Cotransporter 2 Inhibitor

Abstract

The overall goal in the treatment of type 2 diabetes mellitus (T2DM) is remission. However, the effects of a sodium-glucose cotransporter 2 inhibitor (SGLT2i) on remission of T2DM are unknown. We herein report a case involving an overweight 43-year-old man who completely recovered from T2DM after SGLT2i therapy (dapagliflozin at 5 mg/day). In the pretreatment period, he had a body mass index (BMI) of 26.0 kg/m 2 , hemoglobin A1c (HbA1c) concentration of 10.3%, advanced insulin resistance, pancreatic β-cell dysfunction, and fatty liver. Eighteen months after comprehensive therapy, including the administration of an SGLT2i and metformin, his BMI had decreased to 21.3 kg/m 2 and his glycemic control was almost normal (HbA1c of 5.3%) despite discontinuation of all hypoglycemic medications. This report is the first to propose the usefulness of the combination therapy of SGLT2i and metformin for achieving normal body weight and remission of newly diagnosed T2DM in a real-world clinical situation.

A Non-obese, Treatment-Naive Japanese Diabetic Patient With Elevated Insulin Clearance and Hyperglycemia Under Enhanced Insulin Sensitivity and Increased Insulin Secretion: Elevated Insulin Clearance as Type 2 Japanese Diabetes Mellitus (T2JDM)

“…We found that his antibody titer to glutamic acid decarboxylase was undetectable (<5.0 U/mL) and his daily urinary C-peptide immunoreactivity (CPR) excretion was unexpectedly accelerated at 182.07 µg/day, thus establishing a definitive diagnosis of T2DM (Table 4). After admission, we provided the hospitalized dietary (1800 Kcal/day) and exercise therapies according to our standard protocol [8]. On the second day of hospitalization (before treatment), his blood glucose levels were still elevated under the optimal dietary therapy (Table 5).…”

“…Because of the preserved capacity of endogenous insulin secretion from pancreatic β-cells and the absence of insulin resistance, the patient initially received lifestyle modification therapy with stopping smoking and drinking, taking adequate calorie intake, reducing salt intake, and introducing an exercise habit during the hospitalized treatments [8]. He also received an explanation for his diabetic conditions and his novel pathogenesis of hyperglycemia with elevated insulin clearance.…”

“…After discharge, we followed him at our outpatient service as usual [8], which led to an improvement in his blood glucose and glycated hemoglobin (HbA1c) concentrations. In March 2021, his blood glucose, blood pressure, and lipid parameters have been well managed at our outpatient service (fasting glucose; 117 mg/dL, and HbA1c; 6.6 %, blood pressure; 112/71 mmHg, low-density lipoprotein cholesterol; 59 mg/dL, and triglyceride; 75 mg/dL).…”

Quantifying Remission Probability in Type 2 Diabetes Mellitus

“…These effects were observed in spite of the discontinuation of all glucose-lowering medications. This real-world clinical evidence demonstrated that diabetes remission and normal body weight could be effectively achieved in persons with newly diagnosed T2DM by a combination therapy of metformin and SGLT2i [ 48 ].…”

Metformin Intervention—A Panacea for Cancer Treatment?

“…In addition to decreasing blood sugar levels, metformin is emerging as a therapy with other numerous beneficial effects, including body weight control; reductions in the incidence of aging-related diseases; reductions in the risks of cardiovascular and neuropsychiatric disorders and metabolic syndrome; and even improving fertility in polycystic ovary syndrome (PCOS) [ 4 , 5 , 6 , 7 ]. Recent literature data describe metformin as an endothelial protector, an effective drug in heart failure, and an anti-inflammatory target useful in rheumatological and immunological diseases as well as in many aging-related morbidities [ 8 , 9 , 10 ].…”