Healthy lifestyle behaviors, self-management education/support

and social determinants of health should be considered in all patients. Type 2 Diabetes Pharmacotherapy
First-line pharmacotherapy should be selected based Consider early insulin initiation Updated 2023 Treatment Algorithm
upon patient-specific factors: glycemic management with extreme hyperglycemia:
needs, cardiorenal risks, comorbidities, cost and access. - BG ≥300 mg/dL
- A1C >10% Page 1
Consider combination pharmacotherapy at initiation if
- Signs of catabolism
A1C ≥1.5% above target goal.
Page 2
References: American Diabetes Association. Section 9. Pharmacologic Approaches to Glycemic
Treatment: Standards of Medical Care in Diabetes-2023. Individual manufacturer product labels.
Reassess and modify treatment every 3-6 months

Established/High-Risk of ASCVD, Heart Failure, or Chronic Kidney Disease? No Utilize

Selecttherapies
therapieswith
withadequate
adequateefficacy
efficacyto
toachieve
achieveand
andmaintain
maintaintreatment
treatmentgoals.
goals.
In patients with concurrent glycemic management and weight management goals,
Recommended independent of baseline A1C, target A1C goal, or metformin use In patients
consider with concurrent
therapies with highglycemic management
to very high and weight
glucose-lowering and management goals,
weight-loss efficacy.
consider therapies with high to very high glucose-lowering and weight-loss efficacy.

ASCVD Heart Failure Chronic Kidney Disease

(established or high risk) (preserved or reduced EF) (eGFR < 60 mL/min and/or UACR ≥ 30 mg/g)
Glucose-Lowering Weight-Loss
Cost and Access
Efficacy Efficacy
GLP-1 RA or SGLT2i SGLT2i On maximally tolerated ACEi/ARB
with proven CVD benefit with HF benefit
Very High: Very High: Add oral options available
- Avoid TZDs in generic form/lower cost:
- Avoid saxagliptin Dulaglutide (high-dose) Semaglutide
- SU
Semaglutide Tirzepatide - TZD*
SGLT2i with primary evidence for Tirzepatide
High: Consider insulins that are
If A1C above target reducing CKD progression
Insulin available at lower cost:
- May be initiated with an eGFR as low as 20 mL/min Dulaglutide - NPH
- On GLP-1 RA? Consider If A1C above target - Strongest evidence of benefit when UACR ≥ 200 mg/g Combination therapy
Liraglutide - Regular
incorporating SGLT2i - If SGLT2i therapy is contraindicated or not tolerated,
with CVD benefit —— use of a GLP-1 RA with CVD benefit is recommended High: Patient assistance
Intermediate: programs may be available
(and vice versa) GLP-1 RA
GLP-1 RA for certain brand name
- Consider low dose TZD (not listed above)
(not listed above) medications
(avoid in patients with HF) Metformin
SGLT2i *Pioglitazone is available as
If A1C above target SGLT2i generical; rosiglitazone is

Sulfonylurea Intermediate: brand only (Avandia)

On SGLT2i? Consider incorporating GLP-1 RA
(and vice versa) TZD DPP-4i
Metformin
Intermediate:
DPP-4i
CLASS ASCVD HEART FAILURE RENAL

FDA approved CVD benefit: FDA approved HF benefit: FDA approved renal benefit:
SGLT2is • canagliflozin • dapagliflozin • canagliflozin (DKD)
• empagliflozin • empagliflozin • dapagliflozin (CKD)
• empagliflozin (CKD)
Evidence for benefit:
Neutral:
• bexagliflozin* • canagliflozin Neutral: If A1C above target
• dapagliflozin • ertugliflozin • bexagliflozin*
• ertugliflozin • ertugliflozin
Add additional agents based on patient-specific factors including:
GLP-1 RAs & FDA approved CVD benefit: Neutral Evidence for renal benefit: comorbidities, risks, glycemic management needs, convenience, cost and access
GLP-1/GIP RAs • dulaglutide • dulaglutide
• liraglutide • liraglutide Do not combine DPP-4i, GLP-1 RA and/or tirzepatide (GLP-1/GIP RA)
GLP-1/GIP RA tirzepatide
is under investigation for • semaglutide (SUBQ) • semaglutide (SUBQ)
CV and renal benefit
Neutral:
• exenatide ER
• lixisenatide NOTE: Labeled indications and evidence for individual agents are subject to
• semaglutide (oral) frequent change and geographic variability. Last updated 09/2023.

*Bexagliflozin was FDA-approved in 2023 and has limited data suggesting neutral cardiorenal effect. ® 2023 Cosmas Health, Inc. and/or its affiliates. More
Moreclinical
clinicalpearls
pearlsat
atpyrls.com.
pyrls.com
 Page 2 Type 2 Diabetes Pharmacotherapy
Updated 2023 Treatment Algorithm
References:
Comprehensive lifestyle changes and non-insulin agents See Page 1 regarding American Diabetes Association. Section 9.
should generally be considered prior to insulin therapy non-insulin initial Pharmacologic Approaches to Glycemic
pharmacotherapy Treatment: Standards of Medical Care in
Consider early insulin initiation with extreme hyperglycemia: use and selection Diabetes-2023.,
BG ≥300 mg/dL, or A1C >10% or signs of catabolism present Individual manufacturer product labels.

Reassess and modify treatment every 3-6 months to avoid therapeutic inertia

Consider GLP-1 RA or GLP-1/GIP RA in most Already on GLP-1 RA or GLP-1/GIP RA?

Injectable therapy patients prior to insulin GLP-1 RA or GLP-1/GIP RA not appropriate?
needed to lower A1C? Or is insulin preferred?
Titrate to maintenance dose

Assess basal insulin dose

Add basal insulin analog or bedtime NPH based upon patient-specific factors (e.g. cost)
adequacy & evaluate for
overbasalization START: 10 units/day or 0.1-0.2 units/kg/day
Evaluate for clinical signs of TITRATE to fasting plasma glucose (FPG) target:
overbasalization or need for - Follow an evidence-based titration algorithm, e.g. ↑ 2 units every 3 days until FPG target
adjunctive therapy: - Hypoglycemia is never acceptable; titrate at a rate to minimize hypoglycemia risk
- basal dose >0.5 units/kg - If hypoglycemia occurs for no clear reason, ↓ dose 10-20%
- ↑ bedtime-morning/post- — —
--preprandial differential
- hypoglycemia (aware or not)
- high variability
If A1C is above target On bedtime NPH? Consider
conversion to BID NPH
One possible approach:
START:
Add prandial insulin - Total dose = 80% of current
- 2/3 given in the morning
Usually start with one dose with the largest meal or meal with greatest PPG excursion;
prandial insulin can be dosed individually or mixed with NPH as appropriate - 1/3 given at bedtime
TITRATION: Titrate based on
START: the individual’s needs
TITRATION:
- 4 units/day or 10% of basal insulin dose - ↑ dose 1-2 units or 10-15% twice weekly
- If A1C <8%, consider ↓ basal dose by - If hypoglycemia occurs for no clear reason,
——4 units/day or by 10% of basal dose —-↓ dose by 10-20%
If A1C is above target

If A1C is above target Consider BID premix insulin

Stepwise additional
prandial injections
(i.e. 1 then 2 then 3 injections)
Full basal-bolus regimen
(i.e. prandial insulin w/ meals
and basal insulin)
START:
- Usually unit per unit at the - -
- -same total insulin dose, but -
- -may require adjustment for -
Consider self-mixed/split insulin regimen
- -the individual’s needs
Can adjust NPH and short/rapid-acting insulins separately
TITRATION: Titrate based on
START: TITRATION: the individual’s needs
- Total NPH dose = 80% of current NPH - Titrate components
- 2/3 given before breakfast —of the regimen ----
—based on the - - - -
- 1/3 given before dinner —individual’s needs
- Add 4 units of short/rapid insulin to each
——injection or 10% of reduced NPH dose More clinical pearls at pyrls.com

® 2023 Cosmas Health, Inc. and/or its affiliates.