Does glucosamine increase hemoglobin A1c levels or increase the risk of developing new-onset diabetes?

In overweight or obese (ie, high-risk) women, the use of glucosamine for 2.5 years did not increase their likelihood of developing high hemoglobin A1c (HbA1c) levels or receiving a diagnosis of diabetes, either during treatment or over the following 4 years. The study may have been too small to find a difference if one truly exists, but other studies have also failed to find an effect. (LOE = 2b)

Gommans YM, Runhaar J, Jacobs ML, Bierma-Zeinstra SM. The effect of prolonged glucosamine usage on HbA1c levels and new-onset diabetes mellitus in overweight and obese middle-aged women. Am J Med 2017;130:731-737.  [PMID:28011309]

Randomized controlled trial (double-blinded)

Government

Uncertain

Outpatient (primary care)

These researchers studied 354 overweight (34%) or obese (66%) women who were enrolled in a study to prevent knee osteoarthritis. Almost all of them were white and the group had an average age of 55.7 years, The women did not have diabetes at the onset of treatment. They were randomized, allocation concealment unknown, to receive glucosamine sulfate 1500 mg daily or placebo for 2.5 years. After this period, the women discontinued treatment but were followed up for another 4 years. During this time there was significant loss to follow-up and the authors only had data on 55% of the initial enrollees at the end of the 6.5 years. On average, there was no difference between the proportion of patients with elevated HbA1c levels in the 2 groups after 2.5 years of treatment (11.0% vs 18.6%; not significant). At 6.5 years there was no difference between the proportion of women with either high HbA1c levels or a diagnosis of diabetes (8.3% vs 15.2%; not significant). Women with high HbA1c levels at the start of the study but without a diagnosis of diabetes were more likely to have a high HbA1c or a diagnosis of diabetes after 6.5 years, but the study was too small to tell whether the 2 groups were significantly different. Also, given the high number of dropouts over the course of the study and the need to impute missing data, there is still a possibility in my mind that glucosamine could have had an effect.