As with many new medicines, post market surveillance of DTG on a large scale is very important to establish its full safety and side effect profile. This case series contributes to the knowledge about the possible association of hyperglycaemia and DTG treatment. Known factors contributing to hyperglycaemia include reduced insulin secretion, decreased glucose utilization, and increased glucose production, and several medicine, like antihypertensive drugs and protease inhibitors [15]. Additionally, factors like advancing age, male gender, longer duration of HIV infection, low CD4 count, high viral burden, high body mass index, obesity, lower socioeconomic class, comorbidity and drugs should be taking into consideration as contributing factors for hyperglycaemia when it occurs in patient on DTG [16].

A few clinical trial studies and review papers strengthen the evidence that integrase inhibitors (the drug class that DTG belongs to) can induce hyperglycemia [17, 18]. According to VIKING-3, a single armed phase III clinical trial, hyperglycaemia was one of the most common laboratory abnormalities in 14% of the patients at week 48 of integrase strand transfer inhibitor therapy [17].

A case–control study on the incidence of DTG-associated hyperglycaemia in patients with HIV from Uganda also indicates that patients who were transitioned to DTG-based first-line regimens had a higher incidence (16 (0.47%) of 3417 patients) of hyperglycaemia than patients who did not transitioned to DTG 1(0.03%) of 3230 patients in the control group (p = 0.0004) [18]. In literature, there are also a few case reports that support this association. For all the reports, the time to onset of the reaction ranges from 2–5 months after the initiation of the treatment. that has similarities with a study conducted in Uganda which indicates the mean onset of the ADR as 4 months [18]. In a case report, a patient presented to the emergency department (ED) with hyperglycaemia approximately 3 weeks after the switch from EFV to DTG [19].

In contrast to the above findings, the investigation from 4 DTG clinical trials (SPRING-1, STRIIVING, SWORD-1 and -2) on the potential effect of DTG on insulin resistance over time found no association between treatment and insulin resistance observed over a 48 week period [20].

A mechanism for the DTG induced hyperglycaemia is not well understood. However, chelation of magnesium that inhibits the release and signalling of insulin was hypothesized as a mechanism of the toxicity [19]. According to the update of recommendations on first- and second-line antiretroviral regimens issued by the WHO, there is between 3 and 5 kg of unintentional weight gain in individuals receiving DTG-based regimens at 48 weeks, however nothing has been mentioned about hyperglycaemia in relation to the treatment in the update [21]. Hyperglycaemia and weight gain related to DTG are published in the FDA Product information based on clinical trial and post marketing surveillance studies [22]. However, the ADRs are not listed in the Summary of Product Characteristics (SmPC) of the European Medicines Agency (EMA) [23].

The NPC has not received hyperglycaemic cases associated to other HIV medicines during the review period. The SmPC of lamivudine does however include the occurrence of increase in weight and in levels of blood lipids and glucose [23]. Another study on a cohort of 533 HIV-infected and 755 HIV-seronegative men in the Multicentre AIDS Cohort Study evaluated indicates that insulin resistance was seen more commonly among patients with longer exposure to NRTI, in older patients, and in non-white patients (24). Therefore, longer NRTI exposure could have an additive effect to the DTG hyperglycaemic property. The findings of this research will create an opportunity to improve future research on this area and contribute further understanding on DTG-hyperglycaemia association.