Special Clinical Contexts in Diabetes
Agent Selection by Comorbidity · Preferred · Avoid
Drug Selection by Comorbidity: Preferred Agents and Agents to Avoid
ComorbidityPreferred AgentsRationaleAvoid
Established ASCVD GLP-1 RA with CVOT benefit (liraglutide, semaglutide, dulaglutide)
SGLT-2 inhibitor (empagliflozin, canagliflozin)		 MACE reduction proven; independent of HbA1c level Sulfonylureas as first add-on
Chronic Kidney Disease SGLT-2 inhibitor (renoprotection)
Linagliptin (no renal dose adjustment)
GLP-1 RA (most safe in mod CKD)		 Cardiorenal protection persists even when glycemic benefit minimal Glyburide (eGFR <60)
Metformin (eGFR <30)
Heart Failure SGLT-2 inhibitor (all ejection fractions)
GLP-1 RA (stable HF; avoid severe/decompensated)		 SGLT-2: preload/afterload reduction; proven across HFrEF and HFpEF TZDs (fluid retention)
Saxagliptin (HHF signal)
Pregnancy / GDM Insulin (lispro, aspart preferred; NPH for basal)
Metformin (if insulin not feasible)		 Insulin: only agent with established pregnancy safety database; does not cross placenta GLP-1 RA, SGLT-2i, TZDs (insufficient data)
Glyburide (neonatal hypoglycemia)
Elderly / Frail Metformin (if renal function adequate)
DPP-4 inhibitors (weight neutral, low hypo risk)
GLP-1 RA / SGLT-2i (cardiorenal benefit)		 Prioritize hypoglycemia avoidance; relax HbA1c target to 7.5–8.5% by health status Glyburide (Beers Criteria)
Tight HbA1c targets (harm outweighs benefit)
HbA1c Targets in Older Adults (ADA 2024)
  • Healthy: below 7.5% — similar to younger adults
  • Complex / intermediate: below 8.0% — multiple conditions, mild cognitive impairment
  • Very complex / poor health: below 8.5% — end-stage disease, limited life expectancy
  • Consider deprescribing when glycated hemoglobin is well below target
  • Hypoglycemia avoidance is the primary safety goal in frail older adults
Pregnancy and GDM: Key Rules
  • Insulin: standard of care; does not cross placenta
  • GDM targets: fasting <95, 1-hr postprandial <140, 2-hr <120 mg/dL
  • 70–85% GDM managed with diet alone; rest need pharmacotherapy
  • Metformin: crosses placenta — use only when insulin not feasible
  • Insulin requirements double by third trimester; fall abruptly postpartum
  • GDM resolves postpartum but 40–60% develop T2DM lifetime — retest at 6–12 weeks
Emerging Standard for Proteinuric Diabetic CKD
Layer 1
Renin-angiotensin-aldosterone system blockade
(ACE inhibitor or ARB)
+
Layer 2
SGLT-2 inhibitor
(CREDENCE, DAPA-CKD)
+
Layer 3
Finerenone
(FIDELIO-DKD, FIGARO-DKD)
=
Emerging Standard
Maximum cardiorenal protection in diabetic CKD with proteinuria