MOA
↑AMPK & ↓mGPD
leads to:
Metformin
Sulfonylureas
Glinides
↓ hepatic
gluconeogenesis
+
↑ peripheral glucose
uptake
Bind and blocks
ATP-sensitive
K+-channels in β-cells
(= ↑insulin release)
Bind and blocks
ATP-sensitive
K+-channels in β-cells
(= ↑insulin release)
ADME
↓HbA1c
t​1/2​ ≈ 2 hours,
unmetabolized,
and excreted
unchanged by
kidneys.
A:​ Food ↓absrpt
D:​ ≈100% bound to
albumin;
M:​ Hepatic;
E:​ Renal.
D:​ ≈100% bound to
albumin;
M:​ Hepatic;
E:​ Renal.
SGLT-2
inhibitors
Liver metabolism;
↓insulin resistance
+
↑adiponectin
Blocks Na-glucose
cotransport in PCT
≈ 1.5%
↑Glucose-dependent
insulin secretion
↓Glucagon
↓Gastric emptying
DPP-4
inhibitors
↑GLP-1
↑GIP
α-glucosidase
inhibitors
↓Intestinal disaccharide
absorption
Most common side-effects
Less common
side-effects
Yes
(↓GFR = ↑risk for
lactic acidosis)
Yes
(hepatotoxic)
1. GI upset
(​N/V, indigestion, abd.
cramps, bloating, diarrhea);
● ↓B12 (↓gut absrpt);
● ↓Wt.
2. Lactic acidosis.
≈ 1.5%
≈ 1.5%
Yes
Yes
(↓renal excretion =
↑toxicity/s-e)
(↓hepatic metb. =
↑toxicity)
No
No
(adjust dose only)
(adjust dose only)
1. Hypoglycemic rxns
(→ coma);
2. ↑Wt​ (≈ 1-3 kg).
1. Hypoglycemic rxns
(less than w/ SU);
● Sulfa drugs →
hemolytic anemia in
G6PD deficiency pts ±
sulfa allergy;
● Disulfiram-like rxn if
EtOH ingestion.
Not sulfa drugs, Rx if
sulfa allergy.
2. ↑Wt​ (≈ 1-3 kg).
≈ 1%
Contraindications
No
Yes
(just dose
adjustment)
(↓metb ⇒ ↑toxicity)
1. Fluid retention​;
2. ↑Wt​ (≈ 2-4 kg).
● ↓BMD ⇒
↑bone fractures;
● Anemia (dilution, due
to fluid retention);
●
●
●
●
GFR <30;
Liver failure;
Active alcohol abuse;
Unstable or acute HF at risk of
hypoperfusion.
Notes
90% bound to
plasma proteins
0.5 - 1%
Renal excretion
M:​ Hepatic
E:​ Renal
Not metabolized,
excreted
unchanged by
kidneys;
1 - 1.5%
0.5 - 1%
0.5 - 1%
Yes
(diuresis may
↓GFR → AKI)
Yes
(↓metb → ↑toxicity)
No
(adjust dose only)
Yes
1. UTIs;
● Euglycemic DKA;
2. Hypotension.
● ↓BMD → ↑bone
fractures.
No
● Pregnancy and lactation;
● Renal and/or hepatic insufficiency.
● T1DM;
● DKA.
● Active hepatic dz;
● HF;
● Osteoporosis.
● Relative​: Estrogen-containing OCPs
(TZDs ↓their efficacy, ΔRx).
● Frequent UTIs/candidiasis;
● Osteopenia/porosis;
● Foot ulceration;
● Factors predisposing to DKA (eg,
ketosis-prone T2DM, pancreatic
insufficiency, drug or alcohol
addiction).
1. GI upset​ (N/V, diarrhea);
No
Pancreatitis
● Does ​not​ ↓CV or stroke risk.
● T1DM;
● ↑ MI w/ rosiglitazone?
(↓glucose absorption)
GLP-1
agonists
Contraindicated in
hepatic disease?
All factors that ↑risk for lactic acidosis
↑PPAR-γ transcription
leads to:
TZDs
Contraindicated in
renal disease?
GFR <30
2. ↓Wt.
2nd-gen sulfonylureas are
100-200x more potent than
tolbutamide;
Advantage of Glinides over
Sulfonylureas: rapid onset of
action, useful for ​postprandial
glucose excursions​.
● Takes 1-3 months for
maximal effects on glucose
homeostasis;
● Pioglitazone ↓TG, ↑HDL and
LDL ⇒ Rx for NAFLD, even
w/o DM.
● ↓ CVD/HHF;
● ↓ CVD & MI if ASCVD;
● ↓ Prog. of renal disease.
● ↓ CVD/MI/stroke, espec. if
ASCVD;
● ↓ Prog. of albuminuria.
Yes
1. Nasopharyngitis;
2. URIs;
Pancreatitis
Active hepatic disease
↑ risk of HF w/ saxagliptin.
No
Malabsorption-related​ →
undigested CHOs get
fermented ⇒ flatulence,
diarrhea, and pain.
Mild ↑LFTs
GFR <30
Can be used in both T1 and
T2DM.