Anemia and Diabetes Study

Anemia is a common accompaniment to diabetes, particularly in those with albuminuria or reduced renal function. In a study published in The LANCET Diabetes & Endocrinology in November 2020, researchers have reported that canagliflozin reduces the risk of anaemia-associated outcomes, among patients with type 2 diabetes and chronic kidney disease.

Canagliflozin belongs to a class of medications called sodium-glucose co-transporter 2 (SGLT2) inhibitors. It lowers blood sugar by causing the kidneys to get rid of more glucose in the urine. Canagliflozin is not used to treat type 1 diabetes.

The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial was a double-blind, randomized trial in patients with type 2 diabetes and albuminuric chronic kidney disease (CKD) at 690 sites in 34 countries. Between March 24, 2014, and May 5, 2017, 4401 participants were randomly assigned to receive canagliflozin (100 mg; n=2202) or placebo (n=2199). The study findings favoured the use of canagliflozin in patients with type 2 diabetes and kidney disease. Sodium-glucose co-transporter 2 inhibitors might enhance erythropoiesis and increase red blood cell mass. Therefore, Dr. Megumi Oshima, MD and team, conducted a post-hoc analysis of the CREDENCE trial to assess the long-term effects of canagliflozin on anaemia-related outcomes.

Researchers used the linear mixed-effects models to assess the effects of canagliflozin and matched placebo on haemoglobin and haematocrit. The major outcome assessed was a composite outcome of investigator-reported anaemia or treatment for anaemia, which was assessed using Kaplan-Meier analysis and Cox regression models. All analyses were done by intention to treat.

Key findings of the study were:

• At baseline, the researchers noted that the mean haemoglobin concentration was 132·0 g/L (SD 17·7).
• They also noted that about 36% of participants had anaemia, and less than 1% were on erythropoiesis-stimulating agents.
• During a median follow-up period of 2·6 years, they found a rise in the mean haemoglobin concentration (7·1 g/L) and haematocrit level 2·4% among the canagliflozin group than in the placebo group.
• They observed that 573 of 4401 participants had either an investigator-reported anaemia event or the initiation of treatment for anaemia:
  • 358 (8%) of 4401 participants reported anaemia events,
  • 343 (8%) initiated iron preparations,
  • 141 (3%) received erythropoiesis-stimulating agents, and
  • 114 (2%) received a blood transfusion.
• They noted that the risk of the composite outcome of anaemia events or the initiation of treatment for anaemia was lower in the canagliflozin group than the placebo group (hazard ratio 0·65).
• They also noted, compared with the placebo group, participants in the canagliflozin group also had lower risks of anaemia (0·58), initiation of iron preparations (0·64), and need for erythropoiesis-stimulating agents (0·65).

The authors concluded, "These data suggest that canagliflozin reduces the risk of anaemia-associated outcomes, including the need for erythropoiesis-stimulating agents, among patients with type 2 diabetes and chronic kidney disease."

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