1. The Role of SGLT-2 Inhibitors in the Management of Patients with Type 2 Diabetes
Lawrence Blonde, MD
Director, Ochsner Diabetes Clinical Research Unit,
Department of Endocrinology, Diabetes, and Metabolic Diseases
Ochsner Medical Center, New Orleans, LA

2. Disclosures: Lawrence Blonde, MD
Clinical research: Boehringer Ingelheim , Eli Lilly, Johnson & Johnson, Novo Nordisk, Roche, Sanofi-aventis
Advisor or consultant: Amylin, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Halozyme Therapeutics, Johnson & Johnson, MannKind Corporation, Merck, Novo Nordisk, Orexigen Therapeutics, Roche, Sanofi-aventis, Santarus, VeroScience
Speaker/speakers bureau: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Merck, Novo Nordisk, Santarus, VeroScience

3. The Role of SGLT-2 Inhibitors in the Management of Patients with Type 2 Diabetes
This CME activity is supported by an educational grant from:

4. The Role of SGLT-2 Inhibitors in the Management of Patients with Type 2 Diabetes
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5. Case Presentation
48-year-old African American man with 12 month history of type 2 diabetes
Hypertension for past 6 years treated with lisinopril 10 mg daily
Most recent blood pressure was 138/84 mm Hg
Increased LDL-C treated with simvastatin 40 mg qd;
Most recent LDL-C 98 mg/dL
Diabetes treated with lifestyle intervention (increased physical activity, medical nutritional therapy) and metformin 1000 mg bid
Weight 240 pounds, height 6’ (BMI = 32.5)
A1C = 7.5 %

6. Natural History of T2D and β-cell Function
Bergenstal R, et al. Endocrinology. Philadelphia, PA: WB Saunders Co;2001:

7. Ominous Octet
DeFronzo RA. Diabetes. 2009;58:

8. Survival as a Function of A1C in Patients Type 2 Diabetes: A Retrospective Cohort Study*
Oral Agents
Insulin +/- Oral Agents
Currie CJ, et al. Lancet. 2010;6(375):481-9.
*28,000 patients 50 years and older

9. ABCs of Type 2 Diabetes: AACE/ACE 2011 and ADA 2011
Target Treatment Goals
AACE/ACE 2011
ADA 2011
A1C
≤ 6.5%
< 7.0%
Blood pressure
<130/80 mm Hg
Cholesterol (lipids)
LDL-C < 100 mg/dL (< 70 mg/dL for patients with diabetes and coronary artery disease)
HDL-C > 40 mg/dL in men; > 50 mg/dL in women
Triglycerides <150 mg/dL
HDL-C > 40 mg/dL in men; > 50 mg/dL in women;
Triglycerides < 150 mg/dL
*In individuals with overt cardiovascluar disease, a lower LDL-cholesterol goal of <70 mg/dL (1.8 mmol/L), using high-dose of a statin, is an option.
AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. Endocr Pract. 2007;13(suppl 1):1-68.
"Standards of Medical Care in Diabetes—2011." Diabetes Care 34(Supplement 1): S11-S61.
Handelsman Y, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for Developing a Diabetes Mellitus Comprehensive Care Plan. Endocr Pract. 2011;17(Suppl 2):1-53.
Standards of Medical Care in Diabetes—2011. Diabetes Care. 34(Supplement 1): S11-S61.

10. Target Treatment Goals
Glycemic Control Recommendations for Type 2 Diabetes:
AACE/ACE 2011 and ADA 2011
Target Treatment Goals
AACE/ACE 2011
ADA 2011
A1C
≤ 6.5%
< 7.0%
Fasting glucose
Fasting plasma glucose:
< 110 mg/dL
Preprandial capillary plasma glucose: 70 – 130 mg/dL
Postprandial glucose
2-hr postprandial glucose:
< 140 mg/dL
Peak postprandial capillary plasma glucose: < 180 mg/dL
*In individuals with overt cardiovascluar disease, a lower LDL-cholesterol goal of <70 mg/dL (1.8 mmol/L), using high-dose of a statin, is an option.
AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. Endocr Pract. 2007;13(suppl 1):1-68.
"Standards of Medical Care in Diabetes—2011." Diabetes Care 34(Supplement 1): S11-S61.
Handelsman Y, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for Developing a Diabetes Mellitus Comprehensive Care Plan. Endocr Pract. 2011;17(Suppl 2):1-53.
Standards of Medical Care in Diabetes—2011. Diabetes Care. 34(Supplement 1): S11-S61.

11. ADA/AHA/ACC Consensus Recommendations From ACCORD, ADVANCE, & VA Diabetes Trials
A1C goal for non-pregnant adults in general = < 7.0%
Lowering A1C to ≈7.0% has been shown to reduce microvascular and neuropathic complications
For selected individual patients, lower A1C goals may be recommended if goal can be achieved without significant hypoglycemia or other adverse events, eg, patients with
Short duration of diabetes
Long life expectancy
No significant cardiovascular disease
For some patients, less stringent A1C goals may be appropriate, eg, patients with
History of severe hypoglycemia
Limited life expectancy
Advanced microvascular or macrovascular complications
Extensive co-morbid conditions
Long-standing diabetes where goals have not been achieved despite optimal Rx
Skyler J, et al. Diabetes Care. 2009;32:187–192.

12. Challenges in Type 2 Diabetes
Large number of patients
Diabetes affects 25.8 million people (8.3 % of the US population)
DIAGNOSED million people
UNDIAGNOSED- 7.0 million people
PREDIABETES – 79 million people
Progressive worsening of insulin secretory deficit requiring increased number of antihyperglycemic medications over time
Risk for hypoglycemia with some therapies
Risk for weight gain with some therapies
Difficulty controlling postprandial glucose and glucose fluctuations
Preventing and managing complications and co-morbidities
Difficulty attaining and sustaining optimal long-term glycemic control
CDC National Diabetes Fact Sheet. US Department of Health and Human Services.
Cefalu, WT. Am J Med. 2012;343(1):21-26.

13. This is the new landing page of Diabetes HealthSense on the NDEP website.
When you arrive at Diabetes HealthSense, you’ll be directed to a series of options on the left-hand side of the page. The user can select from these options to view and explore the resources within HealthSense that match the criteria you’ve specified. The resources available include more than 140 tools and programs that have been reviewed by a team of behavior change experts who determined the resources’ potential effectiveness and whether or not they should be included in HealthSense.
NDEP’s new video series of real people with diabetes talking about how they manage their diabetes, the struggles they’ve faced, and how they’ve overcome them are available on the Diabetes HealthSense landing page. I will be sharing clips from these later in the presentation.
Below the video player is a list of selected resources for patients that address coping with stress and emotions, healthy eating, being active, and managing your weight. For patients who need help getting started or who are feeling overwhelmed, this is a good place to get started.

14. ADA/EASD Writing Goup Consensus Algorithm
*Validation based on clinical trials and clinical judgment
†Sulfonylureas other than glybenclamide (glyburide) or chlorpropamide
Nathan DM, et al. Diabetes Care. 2009:32:

15. AACE/ACE Diabetes Algorithm for Glycemic Control
American Association of Clinical Endocrinologists. AACE/ACE Diabetes Algorithm for Glycemic Control Available at  Accessed January 2012.

16. Summary of Key Benefits and Risks of Medications
Metformin
DPP-4 Inhibitor
GLP-1 Agonist
Sulfonylurea
Glinide
TZD
Colesevelam
AGI
Insulin
Pramlintide
Benefits
PPG - lowering
Mild
Moderate
Moderate to Marked
FPG - lowering
Neutral
Nonalcoholic fatty liver disease (NAFLD)
Risks
Hypoglycemia
Moderate to Severe
GI Symptoms
Risk of use with renal insufficiency
Severe
Reduce Dosage
Contraindicated if liver failure or predisposition to lactic acidosis
Heart failure/Edema
Contra-indicted in CHF
Mild/ Moderate
Unless with TZD
Contra-indicted in class 1, 4 CHF
Weight Gain
Benefit
Mild to Moderate
Fractures
Drug-Drug Interactions
American Association of Clinical Endocrinologists. AACE/ACE Diabetes Algorithm for Glycemic Control. Available at  Accessed January 2012.

17. Unmet Needs With Conventional Antihyperglycemic Therapies
Many therapies are associated with weight gain
Insulin and non incretin oral insulin secretagogue therapies are associated with significant risk for hypoglycemia
Other AEs with some therapies include GI side effects and edema
Many therapies fail to adequately control postprandial hyperglycemia
Therapies often fail to maintain long-term glycemic control
Blonde L. Am J Manag Care. 2007;13:S36-S40.
Blonde L, et al. J Manag Care Pharm. 2006;12(suppl):S2-S12.
Blonde L, Rosenstock J, Triplitt C. What are incretins, and how will they influence the management of type 2 diabetes? J Manag Care Pharm. 2006;12(suppl):S2-S12.
Blonde L. State of diabetes care in the United States. Am J Manag Care. 2007;13:S36-S40. 17

18. Unmet Needs Type 2 DM Control is Not Durable
Time (months)
Bloomgarden, ZT. Diabtes Care. 2007;30(1):

19. New Classes Presently in Development
Long-acting GLP-1 receptor agonists
Ranolazine
Dual & Pan PPAR agonists
11 Hydroxysteroid Dehydrogenase (HSD)- 1 inhibitors
Fructose 1,6-bisphosphatase inhibitors
Glucokinase activators
G protein-coupled Receptor (GPR)- 40 & -119 agonists
Protein Tyrosine Phosphatase (PTB)- 1b inhibitors
Camitine- Palmitoyltransferase (CPT)- 1 inhibitors
Acetyl COA Carboxylase (ACC)- 1 & -2 inhibitors
Glucagon receptor antagonists
Salicylate derivatives
Immunomodulatory drugs
Sodium- Glucose Cotransporter (SGLT) {-1} & -2 inhibitors

20. The Kidneys Play an Important Role in Glucose Control
Normal Renal Glucose Physiology
180 g of glucose is filtered each day
Virtually all glucose reabsorbed in the proximal tubules & reenters the circulation
SGLT2 reabsorbs about 90% of the glucose
SGLT1 reabsorbs about 10% of the glucose
Virtually no glucose excreted in urine
Mather, A & Pollock, C. Kidney International. 2011;79:S1-S6.

21. Sodium- Glucose Cotransporters
SGLT1
SGLT2
Site
Mostly intestine with some kidney
Almost exclusively kidney
Sugar Specificity
Glucose or galactose
Glucose
Affinity for glucose
High
Km= 0.4 Mm
Low
Km = 2 Mm
Capacity for glucose transport
Role
Dietary glucose absorption
Renal glucose reabsorption
Lee YJ, at al. Kidney Int Suppl. 2007;72:S27-S35.

22. Targeting the Kidney
Chao EC, et al. Nat Rev Drug Discovery. 2010;9:

23. Renal Glucose Transport
Chao, EC & Henry RR. Nature Reviews Drug Discovery. 2010;9:

24. Altered Renal Glucose Control in Diabetes
Gluconeogenesis is increased in postprandial and postabsorptive states in patients with Type 2 DM
Renal contribution to hyperglycemia
3-fold increase relative to patients without diabetes
Glucose reabsorption
Increased SGLT-2 expression and activity in renal epithelial cells from patients with diabetes vs. normoglycemic individuals
Marsenic O. Am J Kidney Dis. 2009;53:
Bakris GL, et al. Kidney Int. 2009;75(12):
Rahmoune H, et al. Diabetes. 2005;54(12):

25. Rationale for SGLT2 Inhibitors
SGLT2 is a low-affinity, high capacity glucose transporter located in the proximal tubule and is responsible for 90% of glucose reabsorption
Mutation in SGLT2 transporter linked to hereditary renal glycosuria, a relatively benign condition in humans
Selective SGLT2 inhibitors have a novel & unique mechanism of action reducing blood glucose levels by increasing renal excretion of glucose
Decreased glycemia will decrease glucose toxicity leading to further improvements in glucose control
Selective SGLT2 inhibition, would also cause urine loss of the calories from glucose, potentially leading to weight loss
Brooks AM, Thacker SM. Ann Pharmacother. 2009;42(7):

26. Effects of SGLT2 Inhibitors
Inhibition of renal tubular Na+- glucose cotransporter
reversal of hyperglycemia
reversal of “glucotoxicity”
Insulin sensitivity in muscle
GLUT4 translocation
Insulin signaling
Insulin sensitivity in liver
Glucose-6-phosphatase
Gluconeogenesis
Decreased Cori Cycle
PEP carboxykinase
Improved beta cell function
DeFronzo RA, et al. Diabetes Obes Metab. 2012;14(1):5-14.

27. SGLT2 Inhibitors in Phase 3 Development
Empagliflozin
Canagliflozin
Dapagliflozin
Ipragliflozin

28. Empagliflozin: Change in A1C
Randomized, double-blind, 12 week trial comparing
empagliflozin and open-label metformin * * *
*P˂.001 vs. placebo
†500 mg BID for four weeks, then 1000 mg BID or the maximum tolerate dose
Ferrannini E, et al. Abstract 877. EASD 2010.

29. Empagliflozin: Change in Plasma Glucose in the Fasting State
Randomized, double-blind, 12 week trial comparing
empagliflozin and open-label metformin * * *
*P˂.001 vs. placebo
†500 mg BID for four weeks, then 1000 mg BID or the maximum tolerate dose
Ferrannini E, et al. Abstract 877. EASD 2010.

30. Empagliflozin Safety Summary
In Phase 2b study
Reported adverse events were comparable among treatment groups
Most frequently reported AEs
Frequent urination, thirst, and nasopharyngitis
Urinary tract infection frequency was low (1.2%) and comparable to placebo (1.2%) and metformin (1.2%)
Incidence of genital infection was low: mycosis (0.8%) and pruritis (1.2%) with Empagliflozin versus none with metformin or placebo
Rates of hypoglycemia were similar between groups
Ferrannini E, et al. Abstract 877. EASD 2010.

31. Metformin + Canagliflozin Dose-Ranging Study
Mean Baseline
A1C (%) * * * * * *
Rosenstock J, et al. Abstract 77-OR. ADA 2010.
*P˂.001 vs. placebo calculated using LS means

32. Canagliflozin SGLT2 Inhibition for Type 2 Diabetes:
Metformin + Canagliflozin Dose-Ranging Study
Mean Baseline
Weight (kg) * * * * * * *
Rosenstock J, et al. Abstract 77-OR. ADA 2010.
*P˂.001 vs. placebo calculated using LS means

33. Canagliflozin Trials
Symptomatic genital infections in 3-8% canagliflozin arms
2% placebo
2% SITA
Urinary tract infections in 3-9% canagliflozin arms
6% placebo
Hypoglycemia in 0-6% canagliflozin arms
5% SITA
Rosenstock J, et al. Abstract 77-OR. ADA 2010.

34. Changes from Baseline in A1C in Phase 3 Dapagliflozin Studies
Placebo Dapa 2.5mg Dapa 5mg Dapa 10mg
Wilding JPH, et al. Abstract 78-OR. ADA 2010; Strojek K, et al. Abstract 870. EASD 2010;
Ferrannini E, et al. Diabetes Care. 2010;33(10): ; Bailey CJ, et al. Lancet. 2010;375(9733):

35. Changes from Baseline in Fasting Plasma Glucose in Phase 3 Dapagliflozin Studies5 -5
mg/dL
-10
-15
-20
-25
-30
Wilding JPH, et al. Abstract 78-OR. ADA 2010; Strojek K, et al. Abstract 870. EASD 2010;
Ferrannini E, et al. Diabetes Care. 2010;33(10): ; Bailey CJ, et al. Lancet. 2010;375(9733):

36. Changes from Baseline in Body Weight in Phase 3 Dapagliflozin Studies
Placebo Dapa 2.5mg Dapa 5mg Dapa 10mg
Wilding JPH, et al. Abstract 78-OR. ADA 2010; Strojek K, et al. Abstract 870. EASD 2010;
Ferrannini E, et al. Diabetes Care. 2010;33(10): ; Bailey CJ, et al. Lancet. 2010;375(9733):

37. Monotherapy Study: Summary and Conclusion
In treatment-naïve patient with newly-diagnosed Type 2 DM, dapagliflozin monotherapy resulted in
Clinically meaningful decreased in A1C and fasting plasma glucose with a near absence of hypoglycemia
Favorable effects on weight and blood pressure
In the exploratory evening dose cohort, changes from baseline in A1C, fasting plasma glucose, and body weight at week 24 were similar to those seen in the main patient cohort
In the high A1C (QAM) exploratory cohort, dapagliflozin elicited a considerable improvement in glycemia
Ferrannini E, et al. Diabetes Care. 2010;33(10):

38. Monotherapy Study: Summary and Conclusion
Increased incidence of urinary tract and genital infections with dapagliflozin treatment:
Events suggestive of urinary tract infection were 4%, 4.6%, 12.5%, and 5.7% for placebo, DAPA 2.5mg, 5mg, and 10mg groups, respectively
Events suggestive of genital infections were 1.3%, 7.7%, 7.8%, and 12.9% for placebo, DAPA 2.5mg, 5mg, and 10mg groups, respectively
Hypoglycemic events occurred in 2.7%, 1.5%, 0%, and 2.9% in patients in placebo, DAPA 2.5mg, 5mg, and 10mg groups, respectively
Ferrannini E, et al. Diabetes Care. 2010;33(10):

39. Dapagliflozin as Add-on Therapy: Summary and Conclusions
Add-on to metformin in patients inadequately controlled with metformin alone
Favorable safety parameters and tolerability
Improved glycemic control
Lowers weight
Not associated with risk for hypoglycemia
Adverse events occurred in similar proportions
Events suggestive of urinary tract infection were 8%, 4%, 7%, and 8% for placebo, DAPA 2.5mg, 5mg, and 10mg groups, respectively
Events suggestive of genital infection were 5%, 8%, 13%, and 9% for placebo, DAPA 2.5mg, 5mg, and 10 mg groups respectively
Hypoglycemic events occurred in 3%, 2%, 4%, and 4% of patients in placebo, DAPA 2.5mg, 5mg, and 10 mg groups respectively
Bailey CJ, et al. Lancet. 2010;375(9733):

40. Dapagliflozin as Add-on Therapy: Summary and Conclusions
Add-on to glimepiride in patients poorly controlled sulfonylurea therapy
Significantly improved mean A1C
Reduced weight
Well-tolerated
Adverse events were similar across all treatment groups
Events suggestive of urinary tract infection were 6.2%, 3.9%, 6.9%, and 5.3% for placebo, DAPA 2.5mg, 5mg, and 10mg groups, respectively
Events suggestive of genital infection were 0.7%, 3.9%, 6.2%, and 6.6% for placebo, DAPA 2.5mg, 5mg, and 10 mg groups respectively
Hypoglycemic events occurred in 4.8%, 7.1%, 6.9%, and 7.9% in patients for placebo, DAPA 2.5mg, 5mg, and 10 mg groups respectively
Strojek K, et al. Abstract 870. EASD 2010

41. Dapagliflozin as Add-on Therapy: Summary and Conclusions
Add-on to insulin in patients poorly controlled with insulin
Sustained effectiveness and stable tolerability
Less likely to D.C or require insulin up-titration due to poor glycemic control versus placebo
Increased frequency of weight loss and reduced frequency of peripheral edema over time
Adverse events and discontinuations were balanced across groups
Actively solicited signs and symptoms suggestive of urinary tract (UTI) and genital infections (GI) were higher with dapagliflozin vs. placebo
Events suggestive of urinary tract infection occurred in 8.4% DAPA vs 4.1% placebo
Events suggestive of genital infection occurred in 7.2% DAPA vs 2.0% placebo
Wilding JPH, et al. Abstract 78-OR. ADA 2010

42. Dapagliflozin* vs. Glipizide as Add-on Therapy to Metformin: 2 Years
Treatment
Change in A1c
≥ 1 Hypoglycemic Episode
Change in Total Body Weight
Dapagliflozin + Metformin (n=315)
-0.32% (-0.42, -0.21)
4.2%
-3.70 kg (-4.16, -3.24)
Glipizide + metformin (n=309)
-0.14% (-0.25, -0.03)
45.8%
(0.88, 1.84)
Urinary tract infection: 13.5% for dapagliflozin; 9.1% for glipizide
Genital infection: 14.8% for dapagliflozin ; 2.9% for glipizide
Nauck MA, et al. Diabetes Care. 2011;34:
*The FDA has not approved this medication for use.

43. Dapagliflozin as Add-on to Metformin: 2 Year Extension Study
Δ from BL (SE)
Placebo
DAPA 2.5mg
DAPA 5mg
DAPA 10mg
A1c, %
0.2 (0.11)
-0.48 (-.1)
-0.58 (0.1)
-0.78 (0.09)
FPG, mg/dl
-10.4 (3.6)
-19.3 (3.2)
-26.5 (2.8)
-24.5 (2.7)
Body weight, kg
-0.7 (0.5)
-2.2 (0.5)
-3.4 (0.4)
-2.8 (0.4)
% Pts with ≥ 1 hypoglycemic event
5.8
3.6
5.1
5.2
Events suggestive of urinary tract infection
Dapagliflozin 2.5 mg: 8.0%, 5 mg: 8.8%, 10 mg: 13.3%
Placebo: 8.0%
Dapagliflozin 2.5 mg: 11.7%, 5 mg: 14.6%, 10 mg: 12.6%
Placebo: 5.1%
Events primarily mild or moderate in intensity and responded to standard treatment
Bailey CJ et al. Abstract 988-P. ADA 2011.

44. Safety: Malignancies Bladder cancer incidence rate:
0.16% patients (n=5,478) treated with dapagliflozin vs 0.03% patients (n-3,156) in placebo group (p = 0.15)
Breast cancer incidence rate:
0.4% patients (n=2,223) treated with dapagliflozin vs 0.09% patients (n=1,053) in placebo group (p = 0.27)
Jones D. Nat Rev Drug Discov. 2011;10(9):

45. Ipragliflozin: Phase 2 Studies
Phase 2, Randomized, Placebo-controlled Study (28 days)
Treatment (n=61)
Change in A1c
FPG(mmol/L)
Change in Total Body Weight
AE’s
Ipragliflozin 50mg QD (n=12)
-0.73% (p<0.003)
-3.35 (p<0.001)
Ipragliflozin (n=48)
-3.2 kg to -4.2kg
vs.
Placebo (n=12)
1.8kg
Constipation, nausea, xerosis, and headache
Ipragliflozin 100mg QD (n=12)
-0.61% (p<0.015)
-2.72 (p<0.004)
Ipragliflozin 200mg QD (n=12)
-0.84% (p<0.001
-3.92 (p<0.001)
Ipragliflozin 300mg QD (n=12)
-3.61 (p<0.001)
Ipragliflozin as add-on Therapy to Metformin
Phase 2, Double-blind, Placebo-controlled, Dose Finding Study (12 weeks)
Treatment (n=272)
(95% CI)
FPG (mg/dL)
Ipragliflozin 12.5mg (n=69)
-0.53%
(-0.71; -0.36)
-8.5
(-16.1; -0.9)
-0.9 ± 2.3
Urinary tract infections and genital tract infections in ipragliflozin groups were no different from placebo group. Hypoglycemia was similar between placebo and treatment groups.
Ipragliflozin 50mg (n=66)
-0.66%
(-0.84, -0.47)
-14.3
(-22.0; -6.6)
-2.1 ± 2.0
Ipragliflozin 150mg (n=66)
-0.72%
(-0.90; -0.54)
-24.3
(-32.1; -16.5)
-2.1 ± 2.4
Ipragliflozin 300mg (n=71)
-0.79%
(-0.97; -0.62)
-27.8
(35.3; -20.3)
-2.3 ± 2.5
Schwartz S, et al. Safety, Pharmacokinetic, And Pharmacodynamic Profiles Of Ipragliflozin (ASP1941), A Novel And Selective Inhibitor Of Sodium-dependent Glucose Co-transporter 2, In Patients With Type 2 Diabetes Mellitus. Diabetes Technology & Therapeutics. 2011; 13(12): Wilding J, et al. Efficacy and safety of ipragliflozin in type 2 diabetes patients inadequately controlled on metformin: a dose-finding study. Abst D IDF 2011.

46. BRIGHTEN Trial: Ipragliflozin
Phase 3, Double-blind, Placebo-controlled Study-16 weeks (n=129)
Ipragliflozin treatment group 50mg QD (n=62)
Ipragliflozin achieved a mean decrease of 1.23% in A1c compared with placebo (p<0.001)
FPG was reduced by 45.8mg/dL compared with placebo (p<0.001)
Total body weight was reduced by 1.47kg compared with placebo (p<0.001)
Similar adverse events occurring in about half the patients in both cohorts.
1 case if hypoglycemia and 2 cases of genital infections in ipragliflozin group
Kashiwagi, A. et al. Ipragliflozin improved glycemic control with additional benefits of reductions of body weight and blood pressure in Japanese patients with type 2 diabetes mellitus: BRIGHTEN Study. Abst 149. EASD 2011

47. Case Presentation 1
48-year-old African American man with 12 month history of type 2 diabetes
Hypertension for past 6 years treated with Lisinopril 10 mg daily;
most recent blood pressure was 138/84 mm Hg
Increased LDL-C treated with simvastatin 40 mg qd;
most recent LDL-C 98 mg/dL
Diabetes treated with metformin 1000 mg bid and lifestyle intervention (increased physical activity, medical nutritional therapy)
Weight 240 pounds, height 6’ (BMI = 32.5)
A1C = 7.5 %

48. Case Presentation 2
64-year-old Latina with 8 year history of type 2 diabetes
Hypertension for past 6 years treated with Olmesartan 10 mg and HCTZ 12 mg daily
most recent blood pressure was 142/86 mm Hg
Increased LDL-C treated with simvastatin 40 mg qd;
most recent LDL-C 98 mg/dL
Diabetes treated with metformin XR 1500 mg QD; insulin glargine 30 U QHS and lifestyle intervention (increased physical activity, medical nutritional therapy)
Weight 160 pounds, height 5’ 2” (BMI = 29.3)
A1C = 7.5 %; FPG

49. Perspectives on SGLT2 Inhibition
Potential advantages
Insulin Independence
Weight loss (75g urine glucose = 300kcal/day)
Low risk of hypoglycemia
Blood pressure lowering?
Concerns
Polyuria
Electrolyte disturbances
Bacterial urinary tract infections
Fungal genital infections
Malignancies