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ADA 2013: Canagliflozin Update

Canagliflozin Added on to Dipeptidyl Peptidase-4 Inhibitors or Glucagon-Like Peptide-1 Agonists With or Without Other Antihyperglycemic Agents in Type 2 Diabetes Mellitus (T2DM)

 

Canagliflozin is an SGLT2 inhibitor which was intended for treatment in diabetic type 2 patients. This analysis was a post hoc design and data was utilized from the Canagliflozin Cardiovascular Assessment Study (CANVAS). This study used patients with a high risk of cardiovascular disease and evaluated their response to canagliflozin 100-300 mg and compared the results with a placebo. A proportion of the subjects in the study were also additionally on a DPP-4 inhibitor (N = 316; mean age, 63 y; A1C, 8.1%; BMI, 32.3 kg/m2) or a GLP-1 agonist (N = 95; mean age, 61 y; A1C, 8.1%; BMI, 37.4 kg/m2). The subjects in the study were then divided into subsets for each concomitant drug as well as divided into monotherapy groups or combination therapy groups. Canagliflozin was administered to the treatment arm for a total of 18 weeks. Those subjects receiving canagliflozin saw a reduction in A1C and body weight relative to the placebo patients in both subsets….

Adverse events were higher in the subjects receiving canagliflozin in comparison to those receiving placebo or DPP-4 inhibitors. Adverse events for canagliflozin were similar to GLP-1 agonists. Serious adverse events were higher with canagliflozin than with placebo in both subsets. Reports of hypoglycemia were also higher with canagliflozin in comparison to placebo for subjects on insulin, sulfonylurea, or meglitinide in the DPP-4i subset (17/70, 29/87, and 12/74) as well as the GLP-1 agonist subset (11/29, 11/22, and 4/26). In conclusion, researchers said that endpoints were addressed and did show that canagliflozin is generally regarded as safe and effective within an 18 week trial period. This study also demonstrated that canagliflozin concomitantly used with a DPP-4 inhibitor or GLP-1 agonists with or without other diabetic medication will reduce patient A1C to varying degrees. Combination therapy with canagliflozin also showed reduced body weight and was well tolerated in type 2 diabetes patients within an 18 week study period.

 

Effects of Canagliflozin Added on to Basal Insulin +/- Other Antihyperglycemic Agents in Type 2 Diabetes 

This analysis uses data from the Canagliflozin Cardiovascular Assessment Study (CANVAS; in T2DM with a history or high risk of cardiovascular disease). The researchers evaluated canagliflozin 100-300 mg versus a placebo in subjects using stable non-titrated basal insulin without the use of prandial insulin (≥30 IU/d basal insulin at study entry) with or without other antihyperglycemic agents (N = 278; baseline mean age, 63 y; A1C, 8.3%; fasting plasma glucose [FPG], 159 mg/dL; BMI, 34.4 kg/m2; insulin dose, 59 IU/d).

The study was conducted for 18 weeks and showed that subjects using canagliflozin had reduced A1C relative to those in the placebo group (-0.86% and -0.89%). Canagliflozin given at 100mg and 300mg reduced FPG (by 25-31 mg/dL) and body weight (by 1.8%-2.7%) versus the placebo group. Post-baseline daily insulin doses (prior to glycemic rescue) were unchanged for 93% of placebo group subjects versus 85% and 86% of subjects with canagliflozin 100 and 300 mg, respectively. Most dose reductions were made with those treated in the canagliflozin arm. Overall, the adverse events that resulted in discontinuation of treatment or serious adverse events were higher in the canagliflozin group compared to placebo. In addition, the proportion of subjects who underwent a hypoglycemic state during the trial (≤70 mg/dL or severe events) was higher in the canagliflozin group compared to placebo (42% 100mg, 43% 300mg , 25% PBO). Severe hypoglycemia occurred at rates of 0%, 1%, and 2%, respectively in the canagliflozin groups in comparison to placebo.

In conclusion to the trial, canagliflozin concomitantly used with basal insulin improved glycemic control, reduced body weight, and was generally well tolerated; however, had some increase in hypoglycemia risk. These results were supported by the data gathered from type 2 diabetics who were studied for an 18 week trial period.

 

Efficacy and Safety of Canagliflozin (CANA) in Subjects With Type 2 Diabetes Mellitus (T2DM) on Metformin (MET) and Pioglitazone (PIO) Over 52 Weeks

This randomized, double-blind study looked at type 2 diabetics using metformin and pioglitazone (N = 342). The study also included a 26-week core period which used canagliflozin 100 and 300 mg in comparison with a placebo as well as a 26-week extension period. Demographics from the 275 patients included in the study were: a mean age of 56.9 y; A1C, 7.9%; fasting plasma glucose 162.2 mg/dL and a BMI 32.5 kg/m2. In the study the placebo group switched to sitagliptin 100 mg. Efficacy data at 52 weeks are reported for canagliflozin 100 and 300 mg and the use of sitagliptin was used to maintain double-blind and as a control group, not as efficacy comparator. At the end of the study period of 52 weeks canagliflozin 100 and 300 mg lowered A1C and FPG from baseline with a significant proportion of subjects reaching A1C <7.0%. Reductions in body weight and systolic BP as well as an increase in HDL-C, LDL-C, and triglycerides were also seen in the canagliflozin arm.

Adverse event rates were lower with canagliflozin 100 mg compared to 300 mg and placebo/sitagliptin groups (70%, 76%, 77%), respectively. Serious adverse events and events that resulted in discontinuations, UTI and hypoglycemia were similar across all trial groups. Higher rates of adverse events related to osmotic diuresis (ie, thirst, pollakiuria; <7% per AE), reduced intravascular volume (ie, postural dizziness, orthostatic hypotension; <2% per AE) and genital mycotic infections were higher in all canagliflozin groups compared to the Placebo/sitagliptin group. In conclusion to the study results, canagliflozin did improve glycemic control, reduce body weight and was generally well tolerated in subjects with type 2 diabetes who were also concomitantly on metformin and pioglitazone over 52 week study period.

 

Canagliflozin (CANA) in Subjects with Type 2 Diabetes Mellitus (T2DM) Inadequately Controlled on Sulfonylurea (SU) Monotherapy: A CANVAS Substudy

Canagliflozin was assessed within the Cardiovascular Assessment Study (CANVAS) and the efficacy, safety and tolerability for type 2 diabetic patients who were inadequately controlled on sulfonylurea monotherapy was studied and assessed (n = 127; 45 placebo, 42 canagliflozin 100 mg and 40 canagliflozin 300 mg). The primary endpoint in the study was to measure the change from baseline HbA1c for an 18 week trail period. Demographics for the study population included: average age 65 years, males (57%), HbA1c 8.4%, BMI 29.9 kg/m2, FPG 10.0 mmol/L, systolic blood pressure(SBP) 136.3 mmHg and eGFR 69.3 mL/min/1.73 m2. When the study groups were broken up at randomization 35% were taking Glimepiride, 29% Glyburide/Glibenclamide and 27% Gliclazide modified release. When results from the study were gathered it showed that canagliflozin at both doses compared to placebo significantly improved glycemic control. Adverse events seen with canagliflozin 100 mg were 26.2% and was lower than placebo recorded at 64.4% and canagliflozin 300 mg at 45%. Adverse events specific to male and female genital infections, pollakiuria and thirst were more common in the canagliflozin groups in comparison to placebo. Adverse events leading to discontinuation of canagliflozin were low with 300 mg at 2.5% and 100 mg at 2.4%. No adverse events leading to discontinuation were reported in the placebo group. Cases of documented hypoglycemia were similar in both the canagliflozin 100 mg (4.1%) and Placebo (5.8%) groups. Higher hypoglycemia was seen in the canagliflozin 300 mg group at 12.5%. Throughout all study groups no severe hypoglycemic episodes were documented.

In conclusion to the study, canagliflozin in addition to sulfonylurea monotherapy gave significant improvements in varies efficacy markers related to type 2 diabetes management. However, use of canagliflozin did show an increased incidence of several specific adverse events such as UTI which the researchers suggested is related to SGLT2 inhibition.

 

Efficacy and Safety of Canagliflozin (CANA) Monotherapy in Subjects With Type 2 Diabetes Mellitus (T2DM) Over 52 Weeks

This study was a randomized, double-blind study which enrolled patients with type 2 diabetes who were currently not controlled with diet and exercise alone. The study included a total of 584 subjects and a placebo group. A 26-week core period using canagliflozin 100 and 300 mg vs placebo and a 26-week extension was also used for the analysis. Subject demographics included 451 total members after exclusion with a mean age of 55.5 y, A1C 7.9%, fasting plasma glucose 165.8 mg/dL, BMI 31.8 kg/m2. The placebo group was also blinded and switched to sitagliptin 100 mg. Efficacy data at 52 weeks was reported for canagliflozin 100 and 300 mg but not for the sitagliptin group which was used only to maintain the double-blind and control groups integrity. At Week 52, canagliflozin showed a dose-related reductions in baseline A1C, FPG and body weight. Use within the canagliflozin group also displayed a decreases in systolic BP and triglycerides as well as an increase in HDL-C and LDL-C.

Adverse event rates for canagliflozin were 67% 100mg, 66% 300mg and 64% with the placebo group and sitagliptin. Serious adverse events related to discontinuations of therapy and hypoglycemia were low across all groups. Genital mycotic infection rates were higher in all canagliflozin groups compared to placebo and sitagliptin. Females had a higher incidence of infection at 10% to 5% compared to males at 8% to 0%. Adverse events related to osmotic diuresis and reduced intravascular volume (≤1% per AE) were seen in the canagliflozin groups at a rates of 5% for 100mg, 8% for 300mg versus 2% for placebo and sitagliptin, UTI rates for canagliflozin 100mg, 300mg and placebo with sitagliptin were 8%, 7%, and 6%, respectively. In conclusion to the trial, canagliflozin monotherapy gave continued improvement in glycemic control and body weight reduction and was generally well tolerated in subjects with type 2 diabetes for the duration of the 52 week study period.

 

Canagliflozin (CANA) Demonstrates Durable Glycemic Improvements Over 104 Weeks versus Glimepiride (GLIM) in Subjects with Type 2 Diabetes Mellitus (T2DM) on Metformin (MET)

This study was a 104 week efficacy and safety analysis of canagliflozin which is the longest follow up study for an SGLT2 inhibitor to date. The design was a randomized, double-blind study using type 2 diabetic patients on metformin (N = 1450; mean age, 56 y; A1C, 7.8%; FPG, 166 mg/dL; BMI, 31 kg/m2; eGFR, 90 mL/min/1.73 m2) who received canagliflozin 100 or 300 mg or Glimepiride (up to 6 or 8 mg/d) during a 52 week core period followed by a 52 week extension phase (n = 1050). At Week 104, both canagliflozin doses reduced A1C, FPG, body weight, systolic BP, and triglycerides compared head to head with Glimepiride with HDL-C and LDL-C increases that were stable from weeks 26 to week 104. Hypoglycemia events occurred less with canagliflozin 100 and 300 mg compared to Glimepiride (7%, 8%, 41%). This study analyzed a coefficient of durability which was defined as the rate of A1C rise from weeks 26 to week 104. The coefficient of durability was lower with canagliflozin at both doses (0.16%) compared to Glimepiride (0.37%)

Adverse event rates were 73%, 78%, and 78% for the canagliflozin groups 100 and 300 mg and Glimepiride, respectively. Serious adverse event rates were similar for all groups as well as discontinuations which was low across all groups. Genital mycotic infection rates were higher in all canagliflozin groups compared to Glimepiride (women, 15% vs 3%; men, 9% vs 2%). A superior decrease in eGFR was seen with Glimepiride (6%) compared to canagliflozin which was roughly ~1-3% at week 104. In conclusion to the study, canagliflozin showed consistent glycemic improvements when compared to Glimepiride and was better tolerated in type 2 diabetic patients on metformin over 104 weeks.

 

Lower Blood Pressure (BP) With Canagliflozin (CANA) in Subjects With Type 2 Diabetes Mellitus (T2DM) 

The BP-lowering response of canagliflozin was evaluated using collected data from 6 randomized, double-blind, placebo controlled Phase 3 studies in subjects with type 2 diabetes (N = 4,158, mean age, 59 y; A1C, 8%; BMI, 33 kg/m2). Canagliflozin in comparison to the placebo only gave modest reductions in systolic BP (SBP; -3.3 and -4.5 mmHg) and diastolic BP (DBP; -1.5 and -1.9 mmHg) in the study subjects. Participants with a SBP ≥140 mmHg (n = 1,267) the reduction seen with both canagliflozin doses in comparison with the placebo showed that the placebo-subtracted decrease was slightly larger with canagliflozin 300 mg compared to what was seen in the overall population and similar to what was seen with canagliflozin 100 mg. In subjects with DBP ≥90 mmHg (n = 355), a greater reduction in DBP was seen with canagliflozin 300 mg against the placebo. The placebo-subtracted decrease was modestly larger with canagliflozin 300 mg compared to the overall population and smaller than canagliflozin 100 mg. Placebo-subtracted BP decreases with both canagliflozin doses were similar among subjects both using and not using antihypertensives agents. Changes in heart rate were -0.6, -0.4, and -0.1 beats per min with canagliflozin 100 and 300 mg and placebo, respectively. The researchers stated that canagliflozin’s glucoretic effect is the reasoning behind a lower incidence of osmotic diuresis adverse events seen with canagliflozin in Phase 3 studies. In conclusion to the study, canagliflozin decreased BP compared to placebo in subjects with a wide range of recorded baseline BP. However, absolute reductions in BP were greater in subjects with higher recorded baseline BP, but placebo-subtracted decreases were similar across groups in the study.

 

Canagliflozin (CANA) Lowers A1C and Blood Pressure (BP) Through Weight Loss-Independent (WL-I) and Weight Loss-Associated (WL-A) Mechanisms

Canagliflozin increases urinary glucose excretion and thus leading to decreased A1C and weight loss in type 2 diabetes patients. Systolic BP may also be decreased due to diuresis and volume loss. Weight loss independent and weight loss associated effects of canagliflozin were estimated using collected data from 4 previously reported 26-week Phase 3 studies (N = 2250). Each study had 3 groups: placebo, canagliflozin 100 mg and canagliflozin 300 mg. Average baseline values for the participants in all groups were: A1C 8.0%, body weight 89 kg, and SBP 128 mmHg. Within each group, mean changes in A1C and SBP were calculated for each decile of weight loss and an ANCOVA analysis was done with ΔA1C or ΔSBP as response and ΔBW (%) as covariate. Greater reductions in A1C and SBP were seen with greater weight loss. Total placebo-subtracted mean reduction in A1C was 0.72% with canagliflozin 100 mg at 0.60% [85%] of the effect was weight loss independent and 0.90% with canagliflozin 300 mg 0.75% [85%] weight loss independent. Total placebo-subtracted reduction in SBP was 3.5 mmHg with canagliflozin 100 mg at 2.0 mmHg [57%] weight loss independent and 4.7 mmHg with canagliflozin 300 mg having a 2.7 mmHg [59%] weight loss independent. However, relative contributions of fat and fluid loss to weight loss association effects cannot be determined from the study. In conclusion, canagliflozin lowers both A1C and BP through weight loss independent and weight loss associated mechanisms with a greater reduction in A1C from weight loss independent compared to SBP.

 

Effect of Canagliflozin (CANA) 300 mg on C-peptide Clearance (CLCpep)

Clinical data has shows that canagliflozin doses ≥100 mg improved indices of β-cell function (βCF) based on circulating C-peptide and glucose concentrations. However, as C-peptide is mostly cleared renally and could be confounded due to alterations in clearance from the use of canagliflozin. Because of this, a 2-period crossover study to assess whether a single 300 mg canagliflozin dose alters CLCpep in 10 healthy subjects was preformed. Demographics of the population included a mean age of 36 years and an average body weight of 79 kg. All patients fasted overnight and then received IV injection of 150 µg of synthetic human C-peptide 3 hours after canagliflozin or placebo was administered 1 hour after starting a constant IV of somatostatin which was used to suppress endogenous C-peptide secretion. Serum C-peptide was measured every 3 hours and patient profiles were fitted to a 2-compartment model to measure CLCpep.

Results showed that serum C-peptide profiles were similar following canagliflozin or placebo treatments. CLCpep was comparable with both canagliflozin and placebo (mean [SD] = 190 [37] vs. 197 [30] mL/min; ratio (CANA/P) [90% CI] = 96% [93%; 99%]). CLR and other kinetic parameters were also comparable between the treatment arms using different strength of canagliflozin. These results demonstrated that canagliflozin 300 mg will not significantly change CLCpep. These results also demonstrate that C-peptide-based measurements of insulin secretion are adequate for checking and monitoring βCF in canagliflozin-treated patients.

 

Efficacy and Safety of Canagliflozin (CANA) in Subjects With Type 2 Diabetes Mellitus (T2DM) and Chronic Kidney Disease (CKD) Over 52 Weeks

This study was a randomized double-blind study designed for type 2 diabetic patients and Stage 3 CKD patients (eGFR ≥30 and <50 mL/min/1.73 m2). out of 269 subjects the demographics included: a mean age of 68.5 years; A1C, 8.0%; fasting plasma glucose of 164.0 mg/dL, BMI, 33.0 kg/m2; eGFR, 39 mL/min/1.73 m2; median albumin/creatinine ratio 30 μg/mg. The subject received canagliflozin 100 or 300 mg or placebo added onto current therapy. 74% of the study population was on insulin during the study. Over 52 weeks, the study results showed that canagliflozin100 and 300 mg decreased A1C, FPG, body weight, and systolic BP and provided small increases in HDL-C as well as decreases LDL-C relative when compared to placebo.

Overall adverse events were 86%, 81% and 87% and serious event rates were 20%, 24%, and 27% with canagliflozin 100, 300 mg and placebo, respectfully. The number of patients who experienced hypoglycemia were 64%, 59%, 46% with canagliflozin 100, 300 mg and placebo, respectfully. Rates of osmotic diuresis-related (eg, pollakiuria; <5% per group) were higher with canagliflozin 100 and 300 mg compared to placebo. UTIs and reduced intravascular volume (eg, postural dizziness) were also higher with canagliflozin compared to placebo. Increases in BUN (12%, 16%, 5%) and decreases in eGFR (-4%, -8%, -3%) and average ACR (-1, -7, 2 μg/mg) were illustrated by canagliflozin 100, 300 mg and placebo, respectfully. In conclusion to the study, canagliflozin did show improved glycemic control and was overall well tolerated in type 2 diabetic and Stage 3 CKD who participated in the study for over 52 weeks. The study results also indicated similar data at 26 weeks.

 

Urinary Tract Infection (UTI) With Canagliflozin (CANA) in Subjects with Type 2 Diabetes Mellitus (T2DM)

Canagliflozin inhibits renal glucose reabsorption which results in increased glucosuria. Subjects with type 2 diabetes were analyzed with canagliflozin or placebo in a phase 3 study with a UTI case report to characterize the presence and severity of new onset infections. The results are reported from a collected analyses from four 26 week studies (DS1; N = 2,313) and participants with moderate renal impairment (eGFR ≥30 and <60 mL/min/1.73 m2) from four 18 to 26 week studies (DS2; N = 1,085) and also from the CANagliflozin Cardiovascular Assessment Study (CANVAS; 52-wk interim safety analysis) in subjects with a high risk of cardiovascular disease (N = 4,327). It should be noted that subjects with a medical history of UTIs were not excluded from these studies and incorporated into the final results.

Analyzing all the data from the combined study populations showed a slightly higher UTI occurrence with canagliflozin with no increase in recurrent or serious events in UTI-related discontinuations. However, upper UTI rates were low and similar across groups populations including placebo. UTI prevalence was more common in women than men, but the increased incidence of UTI with canagliflozin was consistent in both genders. UTIs generally occurred within 26 weeks of starting canagliflozin with incidences becoming less prevalent after that time. Average time to the first symptoms UTI was earlier with canagliflozin; however, average length and severity of UTIs were similar with both canagliflozin and placebo. In conclusion to the study, canagliflozin was correlated with an increase in UTI rates, but no increase in serious or upper UTIs was evident based on the combined type 2 diabetic test population.

 

Genital Mycotic Infections with Canagliflozin (CANA) in Subjects with Type 2 Diabetes Mellitus (T2DM)

Canagliflozin, a sodium glucose co-transporter 2 inhibitor lowers plasma glucose by increasing urinary glucose excretion. Genital mycotic infections with canagliflozin were assessed in subjects with type 2 diabetes mellitus (mean age, 56 y; A1C, 8%; BMI, 32 kg/m2) from 4 randomized, double-blind, 26-wk, placebo (PBO)-controlled studies. Rates of genital mycotic infections were 11% vs. 3% in women and 4% vs. 1% in men with canagliflozin compared to placebo. Genital mycotic infections were generally considered mild or moderate in severity and few led to discontinuation; most events with canagliflozin were treated with antifungal agents (women, 82%; men, 83%).

Canagliflozin-treated women with genital mycotic infections were more likely to have a history of vulvovaginitis (29% vs 12%), be pre-menopausal (35% vs 27%), and reside in North America (60% vs 42%) than those without genital mycotic infections. Canagliflozin-treated men with genital mycotic infections were more likely to have a history of balanitis/balanoposthitis (25% vs 2%), have a slightly longer mean type 2 diabetes mellitus duration (9 vs 7 y), and to reside in Europe (44% vs 26%) than men without genital mycotic infections. With canagliflozin treatment, 2% and 1% of females and males, respectively, had >1 genital mycotic infections.In a larger dataset (from 8 studies with longer mean exposure (canagliflozin, 68 wks; control, 64 wks), a higher rate of male genital mycotic infections was seen (n = 5,493; 8% and 2% for canagliflozin and control), more commonly in uncircumcised than circumcised men (11% vs 3%) and infrequently associated with phimosis or the need for circumcision. In summary, canagliflozin was associated with modestly higher rates of GMIs that were generally manageable with standard treatments.

 

Canagliflozin (CANA) is Effective and Generally Well Tolerated in Subjects with Type 2 Diabetes Mellitus (T2DM) and Stage 3 Chronic Kidney Disease (CKD)

Many patients with type 2 diabetes mellitus have diminished renal function which restrictions the use of current antihyperglycemic drugs. Canagliflozin is a sodium glucose co-transporter 2 inhibitor approved in the United States as an addition to diet and exercise to improve glycemic outcomes in adults with type 2 diabetes mellitus. Canagliflozin is limited to 100 mg with patients with estimated glomerular filtration rate of greater than 45 and less than 60 mls/min/1.73m2 and is not indicated in patients with estimated glomerular filtration rate less than 45 mls/min/1.73m2. Canagliflozin 100 and 300 mg reduced A1C, body weight, and systolic blood pressure compared to placebo in the study population. A1C and body weight was greater in subjects with estimated glomerular filtration rate greater than 45 mls/min/1.73m2 compared to estimated glomerular rate of less than 45 mls/min/1.73m2. Rates of osmotic diuresis – related events were higher in the canagliflozin group compared to placebo in subjects with estimated glomerular filtration rate greater than 30 and less than 60 mls/min/1.73m2. Rate of adverse relate events related to reduced intravascular volume ( postural dizziness, orthostatic hypotension) were higher in the canagliflozin subjects compared to placebo with estimated glomerular filtration rate greater than 30 and less than 60 mls/min/1.73m2. In summary, the subjects with type 2 diabetes mellitus and Stage 3 chronic kidney disease canagliflozin reduced A1C with greater effect in subjects with higher estimated glomerular filtration rate and were generally well tolerated.

 

Efficacy and Safety of Canagliflozin (CANA) in Older Subjects with Type 2 Diabetes Mellitus (T2DM)

Management of type 2 diabetes mellitus in older patients often requires the attention of the effect of advancing age and higher incidence of comorbidities and the risk/benefit of antiglycemic agents. Canagliflozin is a sodium glucose co-transporter 2 inhibitor approved in the United States as an addition to diet and exercise to improve glycemic outcomes in adults with type 2 diabetes mellitus. In a randomized, double-blind, Phase 3 study in older patients with type 2 diabetes mellitus aged 55 to 80 years old canagliflozin reduced A1C and body weight and was generally well tolerated compared with placebo. Overall, adverse events rates were similar in canagliflozin 100 mg 300 mg strengths and placebo in patients aged 55 to 80 years old. Serious adverse events and adverse related events discontinuation rates were similar with canagliflozin 100 mg 300 mg and placebo in subjects less than 65 years old but higher in canagliflozin 100 mg compared to 300mg and placebo in subjects greater than 65 years old. As in subjects less than 65 years old those greater than 65 years old who received canagliflozin had higher rates than placebo of genital mycotic infections in women and men and osmotic diuresis related adverse events. Of the subjects that were randomized and dosed in the overall population, 85.8 percent completed the 26 week treatment period. In summary, canagliflozin 100 and 30 mg improved glycemic control and reduced body weight compared with placebo in subjects with type 2 diabetes mellitus ages 55 to 80 years old.

 

A Health Economic Analysis of the Long-Term Benefits and Associated Cost Offsets of Canagliflozin Monotherapy in the U.S.

In a previous randomized, double-blind, placebo-controlled Phase 3 study involving 584 patients uncontrolled with diet and exercise the use of canagliflozin 100 and 300 mg was shown to significantly decrease HbA1c compared to placebo by 0.91% and 1.16%, respectively. This study simulated how positive changes in measurable biomarkers (HbA1c, body weight, systolic blood pressure, cholesterol) can relate to patient outcomes and future costs.

This study compared treatment algorithms beginning with lifestyle modifications and canagliflozin 100 or 300 mg as monotherapy with one beginning with lifestyle management alone. Baseline patient demographics, biomarker data and treatment effects were recorded from the trial. For patients who had an HbA1c that exceeded 8.0%, the simulated treatment was intensified by adding sulfonylurea and if necessary adding basal insulin and possibly prandial insulin. Alternative regimens were run using metformin as the first rescue therapy. Healthcare needs and total costs associated with microvascular and macrovascular complications were gathered from established clinical resources.

Both algorithms using canagliflozin reduced diabetes complications compared to life-style modifications alone. Reductions for macrovascular events decreased between 5% to 17% and microvascular events up to 36%. The canagliflozin algorithms postponed the start of sulfonylurea administration and insulin use compared to life style modification alone. Over a 1 year period, 20% and 13% of the canagliflozin 100 and 300 mg groups, respectively, needed a sulfonylurea compared to 43% of patients doing life style modification alone. After year 10, only 27% and 19% of the canagliflozin 100 and 300 mg groups, respectively, required insulin compared to 66% of patients using life style modification alone. The final sensitivity analyses showed positive improvements in outcomes associated with the use of canagliflozin and led to lower overall costs and improved quality of life when compared to life style modification lone over a 30 year study period.

Compiled by:
 
David Joffe, BSPharm, CDE, Editor
Jordan Mustonen Doctor of Pharmacy Candidate, University of Florida College of Pharmacy 

Copyright © 2013 Diabetes In Control, Inc.