Sodium glucose co-transporter 2 inhibitors successfully attenuated seasonal change of glycated haemoglobin A1c

Previous studies suggested that glycated haemoglobin (HbA1c) levels are highest in winter and lowest in summer.^1–4 Potential susceptibilities to seasonal change of HbA1c include inappropriate dietary calorie intake and insufficient physical activity in winter. In our hospital, the majority of diabetes patients are farmers and their physical activity is relatively lower in winter (agricultural off-season) than in summer (busy farming season). These patients face difficulties in adapting a seasonal diet modification concomitant with the variation in physical activity.

In this study, we examined the effect of sodium glucose co-transporter 2 (SGLT2) inhibitors on patients who experience seasonal change of their diabetic control. Because those patients also tend to increase body weight, SGLT2 inhibitors were considered as an addition to their current medications to minimise seasonal variation of HbA1c in winter. Our study protocol was reviewed and approved by our hospitals' review boards according to the Declaration of Helsinki. Written informed consent was obtained from each participant. This clinical study involved 30 patients with type 2 diabetes mellitus whose HbA1c showed seasonal change for the previous 3 years and got worse in the autumn of 2015. Patients were prescribed an SGLT2 inhibitor in addition to their current medications. Patients visited the hospital for follow-up examination once a month, and blood glucose levels and HbA1c levels from the same blood samples were measured. In parallel, urinary glucose levels were determined in spot urine samples at each visit. Body weight, blood pressure and estimated glomerular filtration rate (eGFR) were also measured at each visit. Plasma glucose and HbA1c concentrations were determined as previously reported.⁵ The median duration of type 2 diabetes mellitus was 4.7 (range 3.5–18.7) years. All patients reported that they had no infections during the observation period, including any common cold symptoms. We observed no statistically significant change in eGFR, body weight or systolic or diastolic blood pressure after SGLT2 administration.

Seasonal change of HbA1c in the previous 3 years is shown in Fig 1. Their HbA1c was lower in summer and higher in winter before the initiation of SGLT2 inhibitors. SGLT2 inhibitor administration could avoid the tendency for HbA1c to get worse towards winter season as indicated.

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Fig 1.

SGLT2 inhibitor improved seasonal change of HbA1c. Seasonal changes of HbA1c in 30 subjects are shown. The change of HbA1c from summer 2013 was obtained. For summer, we calculated the mean value of three HbA1c measurements from June through August and for winter we calculated the mean value of three HbA1c measurements from December through February. SGLT2 inhibitors were started at the beginning of autumn (mean value from October and December). Error bars represent the standard deviation. The winter HbA1c values were significantly lower in 2015 than 2013 and 2014 (*p<0.05). HbA1c = glycated haemoglobin; SGLT2 = sodium glucose co-transporter 2

Seasonal change of diabetic control triggers treatment difficulties because these variations are usually accompanied by excess calorie intake and a decrement of physical activity.^1–4 If these patients are then administered excess amounts of either endogenous or exogenous insulin without correcting their excess caloric intake and/or improving their decreased physical activity, they will experience inappropriate body weight gain although their blood glucose control may be improved. In this study, we added SGLT2 inhibitors to the patients' current medication and observed whether SGLT2 inhibitor administration could attenuate the tendency for HbA1c to get worse towards winter season. We did not face any hypoglycaemic episodes and body weight gain by the addition of SGLT2 inhibitors. Furthermore, patients experienced neither dehydration nor cerebral infarction. SGLT2 inhibitors are a good option to treat seasonal change of HbA1c levels.

Conflicts of interest

The authors have no conflicts of interest to declare.

Author contributions

TS, EY, YN and SO took care of patients in this study. SO and MY analysed the data and prepared the manuscript.