Author’s reply

Indeed, drug-induced hypoglycemia is one of the most prevalent medication-related harms in comorbid geriatric patients that it is worth being a subject of a debate. In the presented study,1 this iatrogenic syndrome concerned 40 out of 116 patients with diabetes, ie, 34.5% of those taking antidiabetic medications before hospital admission (13.3% of all geriatric study patients). These Figures are extremely high and unbelievable.

Could the type of diabetes have an influence on such a high rate of hypoglycemia? Possibly, it could, but, in clinical practice, the vast majority of older adults has type 2 diabetes.2 Although quite high numbers of individuals with type 1 diabetes are living into old age,3 this discussion concerns the late-onset type 2 diabetes, which is most commonly observed in the older population.4 Differently from middle-aged individuals, diabetes in older people is associated with the combined effects of increasing insulin resistance and impaired pancreatic islet function with aging. Age-related insulin resistance appears to be primarily associated with adiposity, sarcopenia, and physical inactivity.5 Age is one of the main risk factors for type 2 diabetes. For this reason, it was not our intention to differentiate between the 2 types of diabetes in patients at a mean age of over 80 years.

The second point raised by the commentators concerns the risk of hypoglycemia depending on the type of antidiabetic medications used before hospitalization. In my article, separate drugs (metformin, sulfonylureas, insulin) were combined into the joint group of antidiabetic medications, mainly due to the complex treatment and statistical approach. Some detailed data on hypoglycemia depending on the drugs used before hospitalization are presented in Table 1.

Table 1. Drug-induced hypoglycemia by the medication(s) used in 116 diabetic geriatric patients

Drugs

Hypoglycemia (n = 40)

No hypoglycemia (n = 76)

P valuea

Metformin

22 (55)

34 (44.7)

0.29

Sulfonylureas

16 (40)

21 (27.6)

0.17

Any oral antidiabetics

31 (77.5)

45 (59.2)

0.048

Insulin

14 (35)

18 (23.7)

0.2

Any oral antidiabetics + insulin

5 (13)

11 (14)

0.77

Number of drug classes taken before admission

0 (diabetes diagnosed in the hospital)

0

24 (31.6)

<⁠0.001

1

28 (70)

32 (42.1)

2

12 (30)

19 (25)

3

0

1 (1.3)

Data are presented as number (percentage) of patients.

a χ2 Pearson test

The data show that some risks of drug-related hypoglycemia relate to all classes of drugs; to a minor extent to metformin, to a greater extent to sulfonylureas. Surprisingly, oral antidiabetics, irrespectively of classes or numbers, seem to carry an even higher risk of hypoglycemia than insulin itself. The highest proportion of antidiabetic-related harm referred to a single drug item (70% of patients in the hypoglycemic group), which indicates that, more than the type of a drug, the dose makes a difference. Most likely, the oldest patients, unable to visit a specialist regularly, stay a long time on the same (too high) doses of antidiabetics although they actually need lesser doses (due to weight loss, sarcopenia, comorbidity, frailty, etc). They manifest hypoglycemia atypically (fall, confusion, cognitive worsening, syncope, and cardiac arrhythmia). Therefore, according to the American Diabetes Association (2018), the treatment goals include hemoglobin A1c levels below 7.5% for healthy adults with few comorbidities and normal cognitive function and 7.5% to 8.5% for those with multiple comorbidities and cognitive impairment.2