Expert Review of Clinical Pharmacology Downloaded from informahealthcare.com by Nyu Medical Center on 06/04/15 For personal use only.
Key Paper Evaluation
Canagliflozin versus glimepiride treatment in patients with Type 2 diabetes inadequately controlled with metformin (CANTATA-SU trial) Expert Rev. Clin. Pharmacol. 7(1), 21–23 (2014)
Stephen N Davis Department of Medicine, University of Maryland School of Medicine, Physician-in-Chief, University of Maryland Medical Center, 22 S. Greene Street, Room N3W42, Baltimore, MD 21201, USA Tel.: +1 410 328 2488 Fax: +1 410 328 8688 [email protected]
Evaluation of: Cefalu WT, Leiter LA, Yoon KH et al. Efficacy and safety of canagliflozin versus glimepiride in patients with Type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52-week results from a randomized, double-blind, Phase III non-inferiority trial. Lancet 382, 941–950 (2013). The CANTATA-SU study compared two doses of the sodium glucose cotransporter 2 inhibitor canagliflozin (CANA 100 and 300 mg) with the sulfonylurea, glimepiride (6–8 mg) in Type 2 diabetes mellitus patients inadequately controlled on metformin, over 52 weeks. Glimepiride reduced the mean baseline HbA1C from 7.8–6.99%. CANA 100 mg reduced the baseline HbA1C from 7.8–6.98% and CANA 300 mg reduced HbA1C from 7.8–6.87%. Fasting plasma glucose was lowered to a greater extent following CANA 100 mg (1.3 mmol/l) and CANA 300 mg (1.52 mmol/l) as compared to glimepiride (1.02 mmol/l). CANA 100 and 300 mg reduced body weight by 3.7 and 4.0 kg, respectively compared to a 0.7 kg increase with glimepiride. Blood pressure was modestly reduced by both CANA treatments. Both high-density lipoprotein and low-density lipoprotein cholesterol were increased by both doses of CANA compared to glimepiride. Documented hypoglycemia was lower with CANA, but polyuria, pollakiuria, genital mycotic and urinary tract infections were significantly greater in both doses of CANA compared to glimepiride. KEYWORDS: canagloflozin • glimepiride • Type 2 diabetes
Summary of methods & results
CANTATA-SU was a multicenter, randomized, double-blind, controlled trial comparing the efficacy and safety of canagliflozin (CANA) versus glimepiride in Type 2 diabetes mellitus (DM) patients. This was a noninferiority trial. Only if non-inferiority was achieved was superiority then assessed between the two agents. There are several strengths of this study. One of these strengths was that the study was performed double-blind and used an active, relevant comparator. The study was
www.expert-reviews.com
10.1586/17512433.2014.864950
performed in 19 different countries including North America, Europe, Asia and Central or South America. This may explain why the BMI of the participants was ‘only’ 31 kg/m2. The mean age of the participants was 56 years and had a recorded duration of diabetes of approximately 6.5 years. Thus, although it is often difficult to determine the precise time of origin of Type 2 DM in a given individual, the participants in CANTATU-SU would have been expected to have some residual b-cell reserve. The baseline HbA1C was relatively low at 7.8%. This still allowed a
2014 Informa UK Ltd
ISSN 1751-2433
21
Expert Review of Clinical Pharmacology Downloaded from informahealthcare.com by Nyu Medical Center on 06/04/15 For personal use only.
Key Paper Evaluation
Davis
reduction of approximately 0.8% for CANA 100 mg and glimepiride and 0.93% for CANA 300 mg. The HbA1C drop in CANA 300 mg was significantly greater (albeit by only 0.1%) compared to the other two groups and allowed the final mean HbA1C to be below 7% of the CANA 300 mg group. Seven point blood glucose profiles were not provided by the authors. However, both CANA doses resulted in greater reductions in fasting plasma glucose levels as compared to glimepiride. These and previous findings indicate that CANA can lower basal, in addition to postprandial glucose levels [1,2]. As might be expected, the proportion of patients with hypoglycemia (both severe and milder), were lower in the CANA groups compared to glimepiride. CANA also resulted in a significant reduction in body weight (~5.0%) compared to glimepiride. Systolic and diastolic blood pressures were modestly reduced with both CANA doses compared to no change with glimepiride. Importantly, there was no increase in heart rate in either of the two CANA groups. Both CANA doses also resulted in beneficial reductions in triglycerides and increases in high-density lipoprotein. As has been previously noted, there was an increase in low-density lipoprotein (LDL) in both CANA doses. Urinary tract infections (6% for both CANA doses vs 5% for glimepiride dose) and genital infections (9 and 11% for CANA 100 and 300 mg, respectively vs 1.5% for glimepiride) were greater with both CANA doses as was polyuria (3% for both CANA doses vs
Key Paper Evaluation
Canagliflozin versus glimepiride treatment in patients with Type 2 diabetes inadequately controlled with metformin (CANTATA-SU trial) Expert Rev. Clin. Pharmacol. 7(1), 21–23 (2014)
Stephen N Davis Department of Medicine, University of Maryland School of Medicine, Physician-in-Chief, University of Maryland Medical Center, 22 S. Greene Street, Room N3W42, Baltimore, MD 21201, USA Tel.: +1 410 328 2488 Fax: +1 410 328 8688 [email protected]
Evaluation of: Cefalu WT, Leiter LA, Yoon KH et al. Efficacy and safety of canagliflozin versus glimepiride in patients with Type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52-week results from a randomized, double-blind, Phase III non-inferiority trial. Lancet 382, 941–950 (2013). The CANTATA-SU study compared two doses of the sodium glucose cotransporter 2 inhibitor canagliflozin (CANA 100 and 300 mg) with the sulfonylurea, glimepiride (6–8 mg) in Type 2 diabetes mellitus patients inadequately controlled on metformin, over 52 weeks. Glimepiride reduced the mean baseline HbA1C from 7.8–6.99%. CANA 100 mg reduced the baseline HbA1C from 7.8–6.98% and CANA 300 mg reduced HbA1C from 7.8–6.87%. Fasting plasma glucose was lowered to a greater extent following CANA 100 mg (1.3 mmol/l) and CANA 300 mg (1.52 mmol/l) as compared to glimepiride (1.02 mmol/l). CANA 100 and 300 mg reduced body weight by 3.7 and 4.0 kg, respectively compared to a 0.7 kg increase with glimepiride. Blood pressure was modestly reduced by both CANA treatments. Both high-density lipoprotein and low-density lipoprotein cholesterol were increased by both doses of CANA compared to glimepiride. Documented hypoglycemia was lower with CANA, but polyuria, pollakiuria, genital mycotic and urinary tract infections were significantly greater in both doses of CANA compared to glimepiride. KEYWORDS: canagloflozin • glimepiride • Type 2 diabetes
Summary of methods & results
CANTATA-SU was a multicenter, randomized, double-blind, controlled trial comparing the efficacy and safety of canagliflozin (CANA) versus glimepiride in Type 2 diabetes mellitus (DM) patients. This was a noninferiority trial. Only if non-inferiority was achieved was superiority then assessed between the two agents. There are several strengths of this study. One of these strengths was that the study was performed double-blind and used an active, relevant comparator. The study was
www.expert-reviews.com
10.1586/17512433.2014.864950
performed in 19 different countries including North America, Europe, Asia and Central or South America. This may explain why the BMI of the participants was ‘only’ 31 kg/m2. The mean age of the participants was 56 years and had a recorded duration of diabetes of approximately 6.5 years. Thus, although it is often difficult to determine the precise time of origin of Type 2 DM in a given individual, the participants in CANTATU-SU would have been expected to have some residual b-cell reserve. The baseline HbA1C was relatively low at 7.8%. This still allowed a
2014 Informa UK Ltd
ISSN 1751-2433
21
Expert Review of Clinical Pharmacology Downloaded from informahealthcare.com by Nyu Medical Center on 06/04/15 For personal use only.
Key Paper Evaluation
Davis
reduction of approximately 0.8% for CANA 100 mg and glimepiride and 0.93% for CANA 300 mg. The HbA1C drop in CANA 300 mg was significantly greater (albeit by only 0.1%) compared to the other two groups and allowed the final mean HbA1C to be below 7% of the CANA 300 mg group. Seven point blood glucose profiles were not provided by the authors. However, both CANA doses resulted in greater reductions in fasting plasma glucose levels as compared to glimepiride. These and previous findings indicate that CANA can lower basal, in addition to postprandial glucose levels [1,2]. As might be expected, the proportion of patients with hypoglycemia (both severe and milder), were lower in the CANA groups compared to glimepiride. CANA also resulted in a significant reduction in body weight (~5.0%) compared to glimepiride. Systolic and diastolic blood pressures were modestly reduced with both CANA doses compared to no change with glimepiride. Importantly, there was no increase in heart rate in either of the two CANA groups. Both CANA doses also resulted in beneficial reductions in triglycerides and increases in high-density lipoprotein. As has been previously noted, there was an increase in low-density lipoprotein (LDL) in both CANA doses. Urinary tract infections (6% for both CANA doses vs 5% for glimepiride dose) and genital infections (9 and 11% for CANA 100 and 300 mg, respectively vs 1.5% for glimepiride) were greater with both CANA doses as was polyuria (3% for both CANA doses vs
