The Medicines and Healthcare products Regulatory Agency (MHRA) has approved Januvia (sitagliptin) in the UK for use in individuals suffering from moderate to severe renal impairment. As a result, another treatment will be available for individuals with sub-optimum kidney function, who represent up to one third of all those with diabetes.

The approval was based on two 54 weeks studies examining the effectiveness and safety of sitagliptin versus glipizide in patients with moderate to severe renal impairment and type 2 diabetes mellitus (T2D), as well as patients with T2d and end-stage renal disease (ESRD) on dialysis.

In the first study, participants with moderate to severe renal impairment were assigned to receive either 25 or 50 mg once daily of sitagliptin or 2.5 to 20 mg once-a-day of glipizide. Results from the study revealed that after 54 weeks, sitagliptin produced a mean reduction in HbA1c of -0.76% compared with -0.64% with glipizide. Participants in the glipizide group had an incidence of hypoglycemia of 17% compared to only 6.2% in the sitagliptin group, a statistically significant difference.

In the second study, patients with ESRD on dialysis were assigned to receive either 25 mg once daily of sitagliptin for 54 weeks or glipizide. The starting dose with glipizide was 2.5 mg q.d. and titrated up or down to a potential maximum dose of 10 mg b.i.d (20 mg/day). Results from the study showed that sitagliptin provides clinically meaningful reductions from baseline in HbA1c by -0.72% compared with -0.87% with glipizide.

The researchers found that fasting plasma glucose (FPG) was comparable to those seen with glipizide. In addition, sitagliptin was well tolerated and the incidence of symptomatic hypoglycemia was lower than glipizide. However, the researchers found no considerable difference in the incidence of hypoglycemia between the sitagliptin group (6.3%) and the glipizide group (10.8%).

Dr. Donal O’Donoghue, Consultant Nephrologist and lead researcher for the Greater Manchester CLAHRC project CKD theme at the University of Manchester, explained:

“If people with type 2 diabetes have impaired renal function, their kidneys do not filter the blood as efficiently as people with normal kidney function. These patients can pose a management problem because some diabetes treatments are either unsuitable for them, or the dosage must be adjusted dependent upon renal function.

The sitagliptin license extension means that patients with advanced renal impairment, stages 4 and 5 CKD can now be controlled with a simple dosage adjustment. For patients with mild renal impairment no dose adjustment is required, which is a real practical benefit.”

Professor John Wilding, Head of the Department of Obesity and Endocrinology at the University of Liverpool, said:

“One of the main complications of diabetes is kidney disease, or diabetic nephropathy, and this unfortunately develops in up to one third of all people with diabetes. Once the kidneys are damaged due to high levels of blood glucose, early stage kidney disease will follow.

Control of blood pressure and blood glucose can help reduce the risk of kidney disease in people with diabetes, but treatment choices for glucose-lowering treatments are limited because some drugs cannot be used in people with kidney disease, or may increase the risk of hypoglycemia (low blood sugar).

Physicians around the world have been prescribing sitagliptin at 25 mg and 50 mg in this large patient population for a number of years, so it is pleasing that in the UK we now have the option for dosage adjustment to improve glycaemic control, in renally compromised patients with a low risk of hypoglycemia.”

Type 2 diabetes is the most prevalent of the two main types of diabetes (type 1 and type 2) and is responsible for 90% of all people with diabetes. In the UK, 2.9 million individuals are diagnosed with the condition, and an estimated 850,000 individuals have type 2 diabetes by are undiagnosed, as a result it is estimated that in the UK, 2.61 million individuals are affected by the condition.

Approximately one third of individuals with type 1 or type 2 diabetes develop diabetic kidney disease – the most prevalent cause of kidney failure in the UK. Symptoms of diabetic kidney disease include:

  • Swelling of the limbs
  • Fatigue
  • Vomiting
  • Nausea

Written by Grace Rattue