Effectiveness of long-term treatment with SGLT2 inhibitors: real-world evidence from a specialized diabetes center

Abstract

BackgroundDiabetes is a progressive disease needing multiple drugs for achieving and maintaining good glycemic control. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) is a novel class of anti-diabetic agent which offers several beneficial effects. However, the long-term effectiveness in clinical practice and safety data of SGLT2 inhibitors is limited, especially in Asian patients. To better understand the effectiveness of SGLT2i in clinical practice, we conducted a retrospective evaluation of patients with diabetes on SGLT2i.MethodsThis retrospective observational study uses data of patients with diabetes who had been prescribed SGLT2i and continued to use at least 6 months at Theptarin Hospital, Bangkok. The characteristics of patients, changes in glycemic control and body weight at 3, 6, 12, 18, 24 months and the last follow-up were evaluated.ResultsA total of 189 patients with diabetes (females 50.3%, mean age 59.9 ± 12.3 years, T2DM 97.3%, duration of diabetes 16.3 ± 9.2 years, baseline BMI 29.9 ± 6.1 kg/m2, baseline HbA1c 8.8 ± 1.6%) were prescribed SGLT2i during the study period. At the time of first SGLT2i prescription, 80.4% used three or more other anti-diabetic agents concomitantly and 34.6% used insulin concomitantly. 151 patients who continue to use at least 6 months were included in analysis. At the last follow-up (median time 16 months), overall median HbA1c reduction and weight reduction were 1.0% and 1.5 kg, respectively. While glycemic control could maintain up to 18 months, weight loss gradually rebounded after the first 6 months and then backed to baseline body weight at 18 months (78.2 ± 18.0 kg vs. 78.0 ± 17.8, p value = 0.324). The incidence of adverse drug reactions of special interest (polyuria, volume depletion-related events, urinary tract infection, genital infection, and hypoglycemia) was 2.1, 1.6, 2.1, 2.6, and 7.9%, respectively.DiscussionThis real-world study confirmed long-term durability of glycemic control with SGLT2i in not only monotherapy, but also add-on studies with other oral anti-diabetic drugs and/or insulin treatment. However, weight loss became evident early after 6 weeks then reached slightly rebounds after 24 weeks until the end of follow-up. Further studies should be done towards a better understanding of treatment with SGLT2i in routine clinical practice.

Favorable pleiotropic effects of sodium glucose cotransporter 2 inhibitors: head-to-head comparisons with dipeptidyl peptidase-4 inhibitors in type 2 diabetes patients

“…However, our study found fewer differences in body weight changes (− 0.5 kg) in real-world comparisons of SGLT2 inhibitors vs. DPP4 inhibitors. Potentially, the reason may be the complicated disease status and comedications in real-world patients, which may affect the ability to achieve optimal weight reduction from SGLT2 inhibitors [31,32]. Given our observations, the effects of SGLT2 inhibitors and DPP4 inhibitors on weight should be considered when individualizing type 2 diabetes therapy.…”

Excess weight loss in a patient with type 2 diabetes mellitus treated with an SGLT-2 inhibitor

“…the result of a caloric deficit caused by the elimination of glucose and higher renal water excretion (osmotic diuresis). SGLT-2 inhibitors reduced body weight by as much as 4.7 kg [3][4]. Body weight reduction using SGLT-2 inhibitors gradually slows down and becomes stable after 26-34 weeks [5].…”

Cardiorenal protection with SGLT2: Lessons from the cardiovascular outcome trials

“…6 It has been shown that therapy with SGLT2 inhibitors results in a loss of 320-400 kcal/d, with an average weight loss of 3.6 to 4.5 kg in 1 to 2 years. 7,8 Diuresis with therapy averages about 300 cm 3 /d, with a slightly higher amount in the first 24 hours of initiating therapy. 9 Currently, over 50 SGLT2 mutations have been identified, resulting in as much as 150 g/1.73/m 2 /d in loss of urinary glucose.…”

“…SGLT2 inhibitors (‐gliflozins) act by inhibiting renal tubular reabsorption of glucose by inhibition of the SGLT2 protein, which decreases blood glucose, decreases blood pressure, increases water and sodium excretion, and promotes urinary loss of calories in the form of glucose . It has been shown that therapy with SGLT2 inhibitors results in a loss of 320‐400 kcal/d, with an average weight loss of 3.6 to 4.5 kg in 1 to 2 years . Diuresis with therapy averages about 300 cm 3 /d, with a slightly higher amount in the first 24 hours of initiating therapy .…”