ANNOUNCEMENTS

• MONOGRAPH CHECK #2 DUE 10/12 AT 11:59PM

• JOURNAL ARTICLE #3 CHECK DUE 10/19 AT 10:30AM
IN THE NEWS
 Journal Article #2
Efficacy and safety of sotagliflozin in patients with type 2
diabetes and stage 3 chronic kidney disease
Anly Li, PharmD
Regulatory Pharmaceutical Fellow in Drug Information
Purdue University | Eli Lilly and Company | FDA

October 3, 2023
 Objectives
Review background information on diabetes, including current
Review treatment guidelines

Summarize Summarize the sotagliflozin trial

Critique Critique the sotagliflozin trial

Apply Apply the findings of the sotagliflozin trial to a clinical case

 01
Background
Diabetes and Kidney Disease in the United
States

Source: County-Level Distribution of Diagnosed Diabetes Prevalence Among US Adults Aged 20 Years or Older, 2019. [Internet] Centers for Disease Control and Prevention https://www.cdc.gov/diabetes/images/library/reports/nat-state-diabees-trends_fig-3.jpg?_=59190?noicon. (Accessed July 9, 2022).
Diabetes: Key Statistics
Americans with Diabetes

37.3 million
DIAGNOSED DIABETES TYPE 2 DM DIABETIC KIDNEY DISEASE

1.4 million 90-95% 39.2%

1.4 million Americans are 15.7% have CKD stage 3-4
diagnosed with diabetes yearly 5-10% of diabetes diagnoses are
Type 1 diabetes

Centers for Disease Control and Prevention. National Diabetes Statistics Report website. https://www.cdc.gov/diabetes/data/statistics-report/index.html . Accessed September 5, 2023
 T2DM RISK FACTORS

BMI ≥25 kg/m2 45 years or older Family history Sedentary lifestyle

African American,
Gestational Non-alcoholic
Hispanic/Latino, American
diabetes fatty liver disease
Indian, or Alaskan Native

Centers for Disease Control and Prevention. Diabetes Risk Factors. Accessed September 5, 2023.
DIABETES MOA REVIEW

What class of drugs acts on the incretin system?

A. GLP-1 agonists
B. Sulfonylureas
C. TZDs
D. DPP-4 inhibitors
DIABETES MOA REVIEW

What class of drugs acts on the kidneys to decrease glucose

reabsorption?

A. Sulfonylureas
B. SGLT-2 inhibitors
C. Insulins
D. DPP-4 inhibitors
DIABETES MOA REVIEW

What class(es) of drugs acts on the liver to promote

decreased glucose secretion?

A. Sulfonylureas and TZDs

B. SGLT-2 inhibitors and metformin
C. GLP-1 agonists and metformin
D. DPP-4 inhibitors and TZDs
 DIAGNOSIS
Clinical Presentation Signs Laboratory Tests

● Age > 30 years ● Polydipsia, polyuria, ● HbA1c ≥ 6.5%

● BMI > 25 kg/m2 polyphagia are more rare ○ Prediabetes: HbA1c ≥
● Insulin resistance ● Mild fatigue reported 5.7%
● Gradual onset ● Uncommon acute ● Fasting plasma glucose
symptoms and usually ≥126 mg/dL
rare ● Two-hour plasma glucose
● Chronic complications ≥200 mg/dL during OGTT
common ● Random plasma glucose
≥200 mg/dL with
symptoms of
hyperglycemia

Trujillo J, Haines S. Diabetes Mellitus. In: DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Posey L. eds. DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 12th Edition. McGraw Hill; 2023. Accessed September 05, 2023.
https://accesspharmacy.mhmedical.com/content.aspx?bookid=3097&sectionid=269398080
 CHRONIC COMPLICATIONS
Microvascular Macrovascular*

• Attributed to chronic hyperglycemic • Leading cause of death of patients with

state diabetes
• Includes nephropathy, neuropathy, and • Includes coronary heart disease
retinopathy (CHD), ischemic stroke, and peripheral
• Often lead to severe health conditions, artery disease
such as blindness, ESRD, and impaired
wound healing with SSTI infections
• Can be prevented through consistent
glycemic control and annual
screenings • *GLP-1 agonists and SGLT-2
inhibitors recommended
Trujillo J, Haines S. Diabetes Mellitus. In: DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Posey L. eds. DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 12th Edition. McGraw Hill; 2023. Accessed September 05, 2023.
https://accesspharmacy.mhmedical.com/content.aspx?bookid=3097&sectionid=269398080
Microvascular complications of diabetes include which of the following?

A. Neuropathy
B. Retinopathy
C. Nephropathy
D. All of the above
Type II
Diabetes
Management

ElSayed NA, Aleppo G, Aroda VR, et al. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2023. Diabetes Care. 2022;46(Supplement_1):S140-S157. doi:10.2337/dc23-S009
 Clinical ASCVD or multiple
risk factors

Heart Failure

SGLT2 inhibitors
place in diabetes
Minimize Hypoglycemia
therapy

Promote Weight Loss

Chronic Kidney Disease

 GUIDELINE HIGHLIGHTS
Lifestyle behavior changes are key

Pharmacologic therapy selection should be patient-centered

Patients with ASCVD, HF, and/or CKD should be started on cardiorenal

protective agents

Early combination therapy may be considered for some patients

GLP-1 receptor agonists preferred to insulin

American Diabetes Association. Standards of Care in Diabetes—2023 Abridged for Primary Care Providers. Clinical Diabetes. 2022;41(1):4-31. doi:10.2337/cd23-as01
 Diabetic Kidney Disease (DKD)
Diagnosis:
● Elevation of Urinary Albumin Excretion (UACR)
● Low eGFR
● Manifestation of kidney damage

Usually develops after 10 years of T1DM but may already be present at diagnosis of
T2DM
● Screen 1-4 times a year depending on DKD classification
Classification of CKD
GFR Categories Albuminuria Categories
eGFR
Category Terms
mL/min/1.73 m2
A1 A2 A3
G1 > 90 Normal or high
ACR < 30 mg/g 30 - 300 mg/g > 300 mg/g
G2 60-89 Mildly decreased Normal to mildly Moderately
Severely increased
increased increased
Mildly to moderately
G3a 45-59
decreased
Moderately to
G3b 30-44
severely decreased

G4 15-29 Severely decreased

G5 < 15 Kidney failure

 02
SGLT2 Inhibitors
Review of current FDA approved
medications in this class

Source: County-Level Distribution of Diagnosed Diabetes Prevalence Among US Adults Aged 20 Years or Older, 2019. [Internet] Centers for Disease Control and Prevention https://www.cdc.gov/diabetes/images/library/reports/nat-state-diabees-trends_fig-3.jpg?_=59190?noicon. (Accessed July 9, 2022).
SGLT2 products
SGLT inhibitors: “-gliflozins”

Mechanism of action:
inhibit Sodium-glucose cotransporter in the
renal proximal tubule

Initially approved for management of

hyperglycemia in diabetes mellitus
● HF
● CKD
● ASCVD

Source: Chao EC. SGLT-2 inhibitors: A new mechanism for glycemic control. Clinical diabetes : a publication of the American Diabetes Association. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521423/#:~:text=SGLT%2D2%20inhibitors%20have%20a,loss%20and%20blood%20pressure%20reduction. Published January 2014. Accessed September 6, 2023.
 SGLT inhibitors: Effects and Side Effects
Greater impact on postprandial glucose than Side effects:
fasting blood glucose ● Genitourinary Infections
● Diabetic ketoacidosis
A1c lowering (%): ● Volume depletion
● Bexagliflozin: 0.5 – 0.8 ● Hypotension
● Canagliflozin: 0.91 – 1.16 ● Bone fracture
● Dapagliflozin: 0.5 – 0.7 ● Acute kidney injury
● Empagliflozin: 0.7 – 0.9 ● Lower limb amputation
● Ertugliflozin: 0.6 – 0.7 ● Increased LDL Cholesterol
● Fournier’s gangrene
 Dosing guidelines

Hyperglycemia Management
Starting Dose Max Dose eGFR Cut-off

300 mg QD
Canagliflozin 100 mg QD
(100 mg in eGFR 30-60)
< 30 mL/min/1.73 m2

Dapagliflozin 5 mg QD 10 mg QD < 45 mL/min/1.73 m2

Empagliflozin 10 mg QD 25 mg QD < 30 mL/min/1.73 m2

Ertugliflozin 5 mg QD 15 mg QD < 45 mL/min/1.73 m2

Bexagliflozin 20 mg QD 20 mg QD < 30 mL/min/1.73 m2

Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed September 9, 2023. http://online.lexi.com
 Dosing guidelines

Other indications
eGFR cut-off
DKD HF CKD ASCVD in DM
mL/min/1.73 m2

Canagliflozin 100 mga -- -- 100 or 300 mg < 30b

Dapagliflozin 5 mga 10 mg 10 mg -- < 25b

Empagliflozin 10 mgc 10 mg -- 10 mg or 25 mg < 20b

a: approved for urine albumin excretion > 300 mg/day, off-label in < 300 mg/day
b: eGFR cutoff for initiation, continuation of therapy is off-label usage
c: empagliflozin in DKD is an off-label use
 Sotagliflozin (Inpefa)
MOA: inhibits SGLT1 & SLGT2

Indication: reduction of cardiovascular death,

hospitalization for HF, and urgent HF in adults with
HF or T2DM, CKD, and other CV risk factors

Dosing: 200 mg once daily, titrated up to 400 mg

once daily after at least 2 weeks

Adverse Effects:
● Diarrhea
● UTI
● Volume depletion

Inpefa. Package insert. Lexicon Pharmaceuticals Inc; 2023

Danne T, Biester T, Kordonouri O. Combined SGLT1 and SGLT2 Inhibitors and Their Role in Diabetes Care. Diabetes Technology & Therapeutics. 2018;20(S2):S2-69. doi:10.1089/dia.2018.0081
 HALLMARK
TRIALS

SOLOIST-WHF SCORED SOTA-CKD4

• Patients with T2DM and • Patients with T2DM, CV • Patients with T2DM
worsening HF risk factors, and CKD and CKD4

• Primary endpoint: CV • Primary endpoint: CV • Primary endpoint:

death, hospitalization for death, hospitalization for decrease in HbA1c
HF, urgent HF visit HF, urgent HF visit
• Sotagliflozin has no
• Sotagliflozin reduces • Sotagliflozin decreases risk difference versus
cardiovascular risk of primary endpoint placebo on A1c

Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. New England Journal of Medicine. 2021;384(2):117-128. doi:10.1056/NEJMoa2030183
Bhatt DL, Szarek M, Pitt B, et al. Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease. New England Journal of Medicine. 2021;384(2):129-139. doi:10.1056/NEJMoa2030186
Compared to other SGLT2i, which side effect is unique to Sotagliflozin?

A. Urinary tract infections

B. Volume depletion
C. Diarrhea
D. Diabetic ketoacidosis
 Efficacy and safety of sotagliflozin in
patients with type 2 diabetes and stage 3
chronic kidney disease

Cherney DZI, Ferrannini E, Umpierrez GE, et al. Efficacy and safety of

sotagliflozin in patients with type 2 diabetes and stage 3 chronic kidney
disease. Diabetes Obes Metab. 2023;25(6):1646-1657.
doi:10.1111/dom.15019

Source: County-Level Distribution of Diagnosed Diabetes Prevalence Among US Adults Aged 20 Years or Older, 2019. [Internet] Centers for Disease Control and Prevention https://www.cdc.gov/diabetes/images/library/reports/nat-state-diabees-trends_fig-3.jpg?_=59190?noicon. (Accessed July 9, 2022).
METHODS

Study Objective
● Assess the safety and efficacy of
sotagliflozin in adults with type 2
diabetes and stage 3 chronic kidney
disease
METHODS

Study Design
● Multicentered,
randomized, double-blind,
placebo-controlled
● Phase 3 trial
● 150 sites across North and
South America, Europe,
and Asia
METHODS
Inclusion Criteria
● Diagnosis of type 2 DM
● Adults > 18 y/o
● HbA1c 7-11%
● eGFR 30-60 mL/min/1.73m^2
● BMI 20-45 kg/m2
Exclusion Criteria
● SBP > 180 mmHg or DBP > 100
mmHg
● History of diabetic ketoacidosis
(DKA) within 12 weeks
● Renal failure
● Severe hypoglycemia within 6
months
● Use of SGLT2 inhibitor within 12
months
INTERVENTIONS
Treatment Arms:
● Two-week, single-blind run-in period
● Randomized 1:1:1 to receive sotagliflozin 200 mg, 400 mg, or placebo
○ Stratified HbA1c < or ≥8.5%, SBP < OR > 130 mmHg and CKD stage 3A or 3B
● Patients were allowed open-label rescue medications if hyperglycemia occurred
ENDPOINTS
Primary

●HbA1c change from baseline to week 26

Secondary

● Change from baseline to Week 26 in FPG

● Change from baseline to Week 26 in body weight
● Change from baseline to Week 12 in SBP for patients with baseline SBP ≥130 mm Hg
● UACR in patients with a baseline UACR of > 3.4 mg/mmol at week 26
● Proportion of patients with an HbA1c < 6.5% and < 7% at week 26
● Safety over the 52 weeks of treatment
SAFETY
Treatment-emergent adverse events (AEs)

Special interest AEs:

●Cardiovascular events (MACE) ●Genital mycotic infections/UTIs
●DKA ●Volume depletion
●Renal events ●Diarrhea
●Bone fractures ●VTE

Monitoring
●Clinical laboratory values
●Vital sign measurements
●Weight and height
●ECG
●Renal function/urinalysis

ENDPOINTS
STATISTICAL ANALYSIS
Sample size calculation:
● 0.05 α-level
● 130 patients per CKD stratum
○ 99% power (overall) and 98% power (CKD group)
○ Difference in HbA1c of -0.5% (200 mg) and -0.6%
(400 mg)

Intent-to-treat efficacy analysis for all randomized patients

● ANCOVA modeling to evaluate change in HbA1c
○ Covariate = baseline A1c
● Hierarchical testing for superiority

Missing Data: Multiple imputations

● Modeling from same CKD stratum
 Results

Source: County-Level Distribution of Diagnosed Diabetes Prevalence Among US Adults Aged 20 Years or Older, 2019. [Internet] Centers for Disease Control and Prevention https://www.cdc.gov/diabetes/images/library/reports/nat-state-diabees-trends_fig-3.jpg?_=59190?noicon. (Accessed July 9, 2022).
BASELINE DEMOGRAPHICS
787 patients enrolled
● Mean age: 69.5 years
● Female gender: 43.7%
● White: 84.6%
● Duration of diabetes: 17.1 years
● HbA1c%: 8.3%
● BMI: 32.4 kg/m2
● SBP: 140.9 mmHg
● CKD 3A/3B: 50/50%

CKD3B had a higher UACR and greater use

of diuretics and CCB than CKD3A
BASELINE MEDICATIONS

Antihyperglycemics:
● Metformin: 53.7%
● Insulin: 64.3%
● GLP1: 8.4%

Antihypertensives:
● RAAS: 83.4%
● Diuretic: 54.6%

RESULTS
 Similar rates of
discontinuation

RESULTS
ENDPOINTS
Primary:
● Placebo: -0.22 ± 0.06%
● Sotagliflozin 200 mg:
○ –0.32% ± 0.06%
○ –0.10 (–0.25 to 0.05, p=0.2095)
● Sotagliflozin 400 mg:
○ –0.46% ± 0.06%
○ –0.24 (–0.39 to 0.09, p=0.0021)

Secondary:
● Change from baseline to week 26
in FPG (mg/dL)
○ Placebo: -7.2 + 3.6
○ Sotagliflozin 200 mg: –18 ± 3.6, p
= 0.0144
○ Sotagliflozin 400 mg: –16 ± 3.6, p
= 0.0436
● Change from baseline to week 26
in body weight (kg)
○ Placebo: -0.4 + 0.3
○ Sotagliflozin 200 mg: –1.7 ± 0.2, p
< 0.0001
○ Sotagliflozin 400 mg: –1.2 ± 0.3, p
= 0.0155
RESULTS
 SAFETY
● Serious AE:
○ Placebo: 0.8%
○ Sotagliflozin 200 mg: 1.5%
○ Sotagliflozin 400 mg: 0%

Events of special interest (placebo/200/400)

● Genital mycotic infections: 0.8%/1.5%/1.9%
● Diarrhea: 5.8%/7.1%/9.2%
● UTIs: 10.4%/12.7%/10.8%
● Volume depletion: 1.5%/3.0%/3.8%

No events of DKA, renal events in treatment groups

RESULTS
AUTHOR CONCLUSION

● After 26 weeks of treatment, sotagliflozin 400 but not

200 mg treatment significantly reduced HbA1c
compared with placebo in this CKD cohort
● UACR in patients with at least A2 albuminuria was
reduced with each of the two doses at 26 weeks, but the
changes were not sustained at week 52
● Safety findings were as expected
 04
Critique

Source: County-Level Distribution of Diagnosed Diabetes Prevalence Among US Adults Aged 20 Years or Older, 2019. [Internet] Centers for Disease Control and Prevention https://www.cdc.gov/diabetes/images/library/reports/nat-state-diabees-trends_fig-3.jpg?_=59190?noicon. (Accessed July 9, 2022).
Journal
asd
1 Began in 1999

● Interdisciplinary journal
● Focus on clinical and experimental pharmacology and therapeutics

asd
2 Impact Factor (2022): 5.8

● Receives 1300 submissions annually, published monthly

● Acceptance rate of 20%

asd
3 Review Process

● Peer reviewed journal

● Open access
Authors

Dr. David Cherney

● Director of Renal Physiology
Laboratory
● Clinical Scientist in the Division of
Nephrology
● Several publications in DM/DKD
space
Authors
● Director of the USC Clinical
Diabetes Programs
● Multiple publications in
diabetes
● Recipient of the 2020 Banting
Medal for Scientific Achievement
● Did pioneering work in DPP-4 and
SGLT2 inhibition
● Chief of Diabetes and Endocrinology, Grady
Health Systems
● Professor of Medicine, Emory University
School of Medicine, Division of
Endocrinology, Metabolism

David Powell, Michael ● Director of the Dallas Diabetes ● Leader in the area of clinical and
Davies, and Philip Banks Research Center at Medical City translational research in nephrology
are all employees of ● Participated in hundred of clinical ● Has published about 250 papers and reviews
Lexicon Pharmaceuticals trials, has over 470 publications in nephrology

Trial was sponsored by Sanofi and Lexicon Pharmaceuticals which were involved in statistical
analyses, medical writing and editorial assistance
Study Design
Component Impact

Multicenter, multinational ↑ generalizability ↑ external validity

Double-blinded Blinding of investigators and patients reduces bias; ↑

internal validity

Placebo-controlled Gold standard for RCTs; ↑ internal validity

Stratified randomization Reduces confounding; ↑ internal validity

26 week for primary endpoints, Appropriate for assessment of impact on A1c

52 week total duration ↑ external validity
METHODS
Inclusion/Exclusion Criteria Impact
Excluded if change in diabetes medications within 8 Reduces confounding, may ↓ external validity
weeks

Excluded if recent severe hypoglycemia, DKA Appropriate given side effect profile
May ↓ external validity

Other Considerations
● Adherence rates → ↓ internal validity

● Lifestyle changes → ↓ external validity; potential confounding variable

● Rescue medications → Potential confounding variable

● Similar rates of discontinuation → ↑ internal validity

Statistics
Two-sided alpha= 0.05, power set at 99% and 98% Appropriate to minimize risk of type I error (alpha)
and type II error (beta)

Hierarchal testing procedure for superiority Appropriate to assess efficacy and adjust for
multiplicity

ANCOVA modeling for covariate analysis Appropriate for continuous data.

Randomization was stratified by CKD3A/B,
HbA1c, SBP
 Baseline demographics appear balanced
between groups

Fang M, Wang D, Coresh J, Selvin E. Trends in Diabetes Treatment and Control in U.S. Adults, 1999–2018. New England Journal of Medicine. 2021;384(23):2219-2228. doi:10.1056/NEJMsa2032271
 BASELINE DEMOGRAPHICS
Increase external validity Decrease external validity

● Average age 69.5 years ● 84.6% White

● 43.7% female ● 5.2% Black or African American
● BMI 32.4 kg/m2 ● 2.5% Asian
● HbA1c 8.3%
● 25.2% Hispanic or Latino

Average age 69.5 years 43.7% female BMI 32.4 kg/m2

HbA1c 8.3% 84.6% White 5.2% Black or African American

Prevalence of Both Diagnosed and Undiagnosed Diabetes | Diabetes | CDC. Published September 21, 2022. Accessed September 20, 2023. https://www.cdc.gov/diabetes/data/statistics-report/diagnosed-undiagnosed-diabetes.html
 BASELINE MEDICATIONS

Antihyperglycemics: potentially decrease generalizability

● Insulin: 64.4%
● Metformin: 53.7%
● GLP1-RA: 8.4%

Antihypertensives use: increase generalizability

● RAAS: 83.4%
● Diuretic: 54.6%

Fang M, Wang D, Coresh J, Selvin E. Trends in Diabetes Treatment and Control in U.S. Adults, 1999–2018. New England Journal of Medicine. 2021;384(23):2219-2228. doi:10.1056/NEJMsa2032271
ENDPOINTS
Widely
accepted
PRIMARY surrogate
endpoint
● HbA1c change from baseline to week 26

SECONDARY Surrogate
endpoints
● Change from baseline to Week 26 in FPG
● Change from baseline to Week 26 in body weight
● Change from baseline to Week 12 in SBP for patients with baseline SBP ≥130 mm Hg
● UACR in patients with a baseline UACR of > 3.4 mg/mmol at week 26
● Proportion of patients with an HbA1c < 6.5% and < 7% at week 26
● Safety over the 52 weeks of treatment

RESULTS
 ● Results statistically significant for treatment with sotagliflozin
400 mg in overall population and CKD3A
● Clinical significance: change in A1c by 0.5%
○ Results (borderline) clinically significant

● Secondary endpoint:
○ Difference from placebo in A1c at week 52
○ Not statistically significant

Campbell L, Pepper T, Shipman K. HbA1c: a review of non-glycaemic variables. Journal of Clinical Pathology. 2019;72(1):12-19. doi:10.1136/jclinpath-2017-204755
ADVERSE EVENTS
● Discontinuation rate relatively similar
between groups

● Adverse effect profile seen for

sotagliflozin consistent
○ Similar AE to current SGLT2i

● Dose related adverse events:

○ Genital mycotic infections
○ Diarrhea
○ Volume depletion
STRENGTHS

● Stratified randomization, double-blinded, multicentered

● Primary endpoint (HbA1c) is a well-established surrogate
● 26 week treatment period + 26 week extension period appropriate
● Use of intent-to-treat analysis
● 200 mg and 400 mg are approved doses for sotagliflozin
● 4-week safety follow-up period at the end of the trial
● Average age of 69 years, baseline BMI of 32.4 kg/m 2
● Similar representation of women (43.6%) and men (56.4%)
LIMITATIONS

● Predominately white (84.6%) subjects

● Drugs names and doses of rescue medications were not provided
● No mention of lifestyle modifications
● No discussion of adherence & drop out rates
● Patients excluded if change in antidiabetic drugs within 8 weeks
● No discussion of number of patients excluded during screening or run-in period
● 8.4% of patients were on a GLP1-RA but that is a first line therapy now
● Results not clinically significant and not sustained at week 52
Study Implications
Generalizability

Children Adults

Male Female

Patients with:

CKD1 CKD2 CKD3 CKD4 CKD5

T1DM T2DM

BMI 20-25 BMI 30-35 BMI > 45

 Impact on Practice

● Does Sotagliflozin address an

unmet therapeutic need in current
guidelines?
● How does sotagliflozin compare to
other SGLT2 inhibitors?
○ Side effects?
○ Cost?
● What place in therapy could
sotagliflozin have in diabetes
management?
 Conclusion

● Sotagliflozin 400 mg decreases HbA1c at week

26 but the effect is not sustained at week 52
○ Diabetes is a chronic disease - is a 26 week
decrease in A1c clinically relevant?

● Compared to other SGLT2 inhibitors,

sotagliflozin does not show an increased benefit
○ Bexagliflozin, canagliflozin, empagliflozin
can be used in eGFR up to 30
mL/min/1.73m2

● Sotagliflozin has a similar cost and side effect

profile compared to other SGLT2 inhibitors
 05
Patient Case

Source: County-Level Distribution of Diagnosed Diabetes Prevalence Among US Adults Aged 20 Years or Older, 2019. [Internet] Centers for Disease Control and Prevention https://www.cdc.gov/diabetes/images/library/reports/nat-state-diabees-trends_fig-3.jpg?_=59190?noicon. (Accessed July 9, 2022).
 Case Study
You are a pharmacist working at an ambulatory care clinic and
Age: 65
specialize in diabetes management. Your patient NJ, is a 65-year old
CrCl: 39 mL/min male who was diagnosed with T2DM in 2007. His primary care
provider is interested in adding on an additional medication. He
A1c: 8.3%
recently heard about a new drug, sotagliflozin, and is curious if it
BP: 143/79 would be a good therapy for NJ. What would you recommend?

BMI: 39.3
PMH, lab values, and current medications are as listed.
PMH: UTI (5/23), HTN, Obesity, MI (2015), HF
A.Continue current therapy of metformin, lantus, and glipizide
Current medications: B. Continue current therapy and add sotagliflozin 200 mg daily
● Metformin 1000 mg twice daily C. Continue current therapy, add empagliflozin 10 mg daily
● Lantus 35u SQ at bedtime D. Discontinue metformin and add sotagliflozin 400 mg daily
● Glipizide 10 mg once daily
● Atorvastatin 80 mg at bedtime
● Lisinopril 40 mg once daily
● Spironolactone 50 mg once daily
 Case Study 2

You are a pharmacist working at the FDA. Based on the results of this study,
would you approve sotagliflozin for use in hyperglycemia/diabetes
management in patients with CKD 3?

A. Yes both sotagliflozin 200 mg and 400 mg

B. Yes, only sotagliflozin 200 mg
C. Yes, only sotagliflozin 400 mg
D. No
What Questions do you have Questions?
for me?

li4970@purdue.edu
 ANNOUNCEMENTS
• MONOGRAPH CHECK #2 DUE 10/12 AT 11:59PM
• JOURNAL ARTICLE #3 CHECK DUE 10/19 AT 10:30AM