Major Research Findings

Ertugliflozin has been shown to be effective in improving glycemic control in Asian patients with type 2 diabetes who are inadequately controlled on metformin monotherapy, according to a phase III, randomized, double-blind study 1 , which also included evaluation in the China subpopulation.

Ertugliflozin has been shown to help improve glycemic control in patients with type 2 diabetes. 4 provides a detailed explanation of the mechanism of action of SGLT2 inhibitors and the current state of research exploring naturally-derived compounds that can improve glycemic control.

Reasons for Side Effects

SGLT2 inhibitors work by inhibiting glucose reabsorption in the kidneys, increasing glucose excretion in the urine. This mechanism of action leads to lower blood glucose levels, but can also cause side effects. 2 provides a detailed explanation of the mechanism of action of SGLT2 inhibitors and their clinical applications. Additionally, 3 provides a safety update on SGLT2 inhibitors, including a detailed explanation of the risks of side effects.

Common Side Effects

Genital Candidiasis

The most frequent side effect is genital mycotic infections with candida species that are usually mild to moderate in severity, easily treated and infrequently recur. 3 .

Urinary Tract Infections

Urinary tract infections, although common in patients with diabetes, have not been shown to be increased in controlled studies with SGLT2i. 3

Hypoglycemia

Hypoglycaemia can occur when an SGLT2i is added to agents that cause hypoglycaemia, such as insulin or sulphonylureas. 3

Volume Depletion and Hypotension

Volume depletion and hypotension is infrequent and can be minimized by adjusting diuretic and antihypertensive treatment in patients at risk. 3

Acute Renal Failure or Kidney Injury

Acute renal failure or kidney injury was observed in early observational studies. However, in randomized controlled trials (RCTs) and in more recent observational studies a decreased incidence of acute kidney injury was observed in SGLT2-treated patients compared to those receiving either placebo or another class of glucose lowering agents. 3

Amputation

An increased incidence of amputation (largely feet and toes) was observed in the RCT with canagliflozin but not with the other SGLT2i. Observational studies have shown either an increased risk of amputation with other agents whereas another study showed no increase. Although the increased risk of amputation is very low, avoidance of SGLT2i in patients at high risk seems prudent. 3

Fractures

Increased incidence of fractures was observed with canagliflozin but not with SGLT2i nor in a meta-analysis that included canagliflozin, empagliflozin and dapagliflozin. 3

Cancer

No increased incidence of cancer has been observed in either RCTs or observational studies. 3

Side Effect Management

Genital Candidiasis

Genital candidiasis can be treated with antifungal medication. Maintaining good hygiene of the vagina and penis is important to prevent recurrence. 3

Hypoglycemia

To minimize the risk of hypoglycemia, it is important to monitor blood glucose levels regularly and adhere to dietary and exercise recommendations. Additionally, caution is necessary when combining these drugs with agents that can cause hypoglycemia, such as insulin or sulfonylureas. 3

Volume Depletion and Hypotension

Patients at risk of volume depletion and hypotension should have their diuretic and antihypertensive medications adjusted as instructed by their doctor. 3

Amputation

Patients at high risk for amputation should undergo regular foot and toe examinations as instructed by their doctor. Wearing appropriate shoes and keeping the feet clean is important to maintain foot and toe health. 3

Fractures

Patients at high risk for fractures should undergo screening for osteoporosis and take calcium and vitamin D to maintain bone health. 3

Comparison Between Studies

Commonalities

All of these studies suggest that SGLT2 inhibitors may be effective in improving glycemic control in patients with type 2 diabetes.

Differences

These studies investigated different SGLT2 inhibitors and had different patient populations. Additionally, different side effects were reported in these studies.

Considerations for Real-World Application

SGLT2 inhibitors are effective medications for the treatment of type 2 diabetes. However, it is important to remember that these drugs can cause side effects. If you are considering taking SGLT2 inhibitors, discuss the risks and benefits with your doctor.

Limitations of Current Research

Further research is needed to determine the long-term safety and effectiveness of SGLT2 inhibitors. Additionally, further research is needed to evaluate how these drugs affect different patient populations.

Future Research Directions

Future research should evaluate the long-term safety and effectiveness of SGLT2 inhibitors, and evaluate the impact of these drugs on different patient populations. Additionally, it is necessary to investigate new applications for these drugs.

Conclusion

SGLT2 inhibitors are promising drugs for the treatment of type 2 diabetes. These drugs may improve glycemic control. However, it is important to remember that these drugs can cause side effects. If you are considering taking SGLT2 inhibitors, discuss the risks and benefits with your doctor.