First-line therapy should be selected based upon

patient-specific factors: glycemic management needs,

Consider early insulin Type 2 Diabetes Pharmacotherapy
initiation with extreme
risks, comorbidities, cost, and access. Generally includes hyperglycemia: Updated 2022 Treatment Algorithm
metformin and comprehensive lifestyle changes. BG >300, or A1C >10%,
Consider combination pharmacotherapy or signs of catabolism Page 1
at initiation if A1C ≥1.5% above target goal present
(e.g. metformin + additional agent). Page 2
References: American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment:
Standards of Medical Care in Diabetes-2022., Individual manufacturer product labels.
Reassess and modify treatment every 3-6 months

High-risk indicators or established ASCVD, HF, or CKD? No If A1C is above individualized target goal

Recommended independent of baseline A1C, target A1C goal, or metformin use Utilize agents/combinations that provide adequate efficacy to reach and maintain
glycemic goals, while considering additional patient-specific factors in choice of
therapy including: comorbidities, risks, convenience, cost and access
High-risk indicators or
Heart Failure Chronic Kidney Disease
established ASCVD (e.g. eGFR < 60)

GLP-1 RA or SGLT2i SGLT2i CKD + albuminuria CKD without Need to Minimize Need to Promote
with HF benefit Cost and Access
with proven CVD benefit (≥300 mg/g creatinine) albuminuria Hypoglycemia Risk Weight Loss
-Avoid TZDs
-Avoid saxagliptin
Low/no hypoglycemia risk: Preferred: GLP-1 RA Add options available in
- DPP-4i with weight loss efficacy generic form/lower cost:
Preferred: an SGLT2i SGLT2i or
If A1C above target
(e.g. SQ semaglutide, dulaglutide) - SU
with primary evidence GLP-1 RA - GLP-1 RA
for reducing CKD w/ CVD benefit Alternate: SGLT2i - TZD*
- SGLT2i
- On GLP-1 RA? Consider If A1C above target progression - Consider insulins that are
- TZD available at lowest cost
incorporating SGLT2i with
Alternate: SGLT2i
CVD benefit and vice versa with evidence for SU and insulins have notable *Pioglitazone is available
- Consider low dose TZD reducing CKD If A1C above target hypoglycemia risk generically; rosiglitazone is
(avoid with HF) progression in CV - Later generation SUs have less
If A1C above target brand only (Avandia)
outcomes trials On SGLT2i? hypoglycemia risk
Consider On GLP-1 RA? Consider
- Basal insulin hypoglycemia risk:
If SGLT2i not tolerated, incorporating
degludec, glargine U300 < glargine incorporating SGLT2i
use GLP-1 RA with GLP-1 RA and
CVD benefit
U100, detemir < NPH insulin and vice versa
vice versa
If GLP-1 RA not tolerated/
indicated, consider DPP-4i

CLASS ASCVD HEART FAILURE RENAL

SGLT2is FDA approved CVD benefit: FDA approved HF benefit: FDA approved renal benefit:
• canagliflozin • dapagliflozin • canagliflozin (DKD) If A1C above target
• empagliflozin • empagliflozin • dapagliflozin (CKD)
Neutral: Evidence for benefit: Evidence for benefit:
• dapagliflozin • canagliflozin • empagliflozin Add additional agents based on patient-specific factors including: comorbidities, risks,
• ertugliflozin • ertugliflozin glycemic management needs, convenience, cost, and access
GLP-1 RAs FDA approved CVD benefit: Neutral Evidence for renal benefit: Do not combine DPP-4i and GLP-1 RA
• dulaglutide • dulaglutide
• liraglutide • liraglutide
• semaglutide (SQ) • semaglutide (SQ)
Neutral:
• exenatide ER
NOTE: Labeled indications and evidence for individual agents are subject
• lixisenatide
to frequent change and geographic variability. Updated 12/2021.
• semaglutide (oral)
® 2022 Cosmas Health, Inc. and/or its affiliates. More clinical pearls at pyrls.com.
 Page 2 Type 2 Diabetes Pharmacotherapy
Updated 2022 Treatment Algorithm
References: American Diabetes Association. 9.
Comprehensive lifestyle changes and non-insulin agents See Page 1 regarding Pharmacologic Approaches to Glycemic Treatment:
should generally be considered prior to insulin therapy non-insulin initial Standards of Medical Care in Diabetes-2022.,
pharmacotherapy Individual manufacturer product labels..
Consider early insulin initiation with extreme hyperglycemia: use and selection
BG >300, or A1C >10%, or signs of catabolism present

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

Injectable therapy Consider GLP-1 RA in most prior to insulin Already on GLP-1 RA? or GLP-1 RA not
needed to lower A1C? Titrate GLP-1 RA to maintenance dose appropriate? or is insulin preferred?

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
TITRATE to fasting plasma glucose (FPG) target:
Evaluate for clinical signs of - Follow an evidence-based titration algorithm, e.g. ↑ 2 units every 3 days until FPG target
overbasalization or need for - Hypoglycemia is never acceptable; titrate at a rate to minimize hypoglycemia risk
adjunctive therapy: basal dose
- If hypoglycemia occurs for no clear reason, ↓ dose 10-20%
>0.5 units/kg, ↑ 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: individual 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 4 - If hypoglycemia occurs for no clear reason,
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

START:
- Usually unit/unit at the same total
insulin dose, but may require
Stepwise additional Consider self-mixed/split insulin regimen adjustment to individual needs
prandial injections Can adjust NPH and short/rapid-acting insulins separately TITRATION: Titrate based on
(i.e. 1 then 2 then 3 injections) individual needs
START: TITRATION:
- Total NPH dose = 80% of current NPH - Titrate components
- 2/3 given before breakfast of the regimen based
on individual needs
Full basal-bolus regimen - 1/3 given before dinner
- Add 4 units of short/rapid insulin to each
(i.e. basal and prandial
injection or 10% of reduced NPH dose More clinical pearls at pyrls.com
insulin with each meal)
® 2022 Cosmas Health, Inc. and/or its affiliates.