The document presents a comprehensive table detailing various glucose-lowering medications and therapies for adults with type 2 diabetes, including their physiological actions, advantages, disadvantages, and efficacy levels. It categorizes treatments into classes such as oral medications, injectable medications, and weight loss therapies, highlighting their impact on glucose control and associated risks. The information serves as a guide for individualized treatment choices based on patient needs and circumstances.

1. Table 2—Glucose-lowering medications and therapies available in the U.S. or Europe and specific characteristics that may guide individualized treatment choices in
nonpregnant adults with type 2 diabetes
Class
Medications/therapies
in class Primary physiological action(s) Advantages Disadvantages/adverse effects Efficacy
Lifestyle
Diet quality c Mediterranean type
c DASH
c Low carbohydrate
c Vegetarian
c Others
c Depends on diet c Inexpensive
c No side effects
c Requires instruction
c Requires motivation
c Requires lifelong behavioral change
c Social barriers may exist
Intermediate
Physical activity c Running, walking
c Bicycling (including
stationary)
c Swimming
c Resistance training
c Yoga
c Tai chi
c Many others
c Energy expenditure
c Weight management
c ↑ Insulin sensitivity
c Inexpensive
c ↓ Fall risk by increasing balance/strength
c ? Improves mental health
c ↑ Bone density
c ↓ Blood pressure
c ↓ Weight
c Improves ASCVD risk factors
c Risk of musculoskeletal injury
c Requires motivation
c Risk of foot trauma in patients with
neuropathy
c Requires lifelong behavioral change
Intermediate
Energy restriction c Individual energy
restriction with or
without energy tracking
c Programs with
counseling
c Food substitution
programs
c Energy restriction
c Weight management
c ↓ Hepatic and pancreatic
fat
c ↑ Insulin sensitivity
c Lowers glycemia
c Reduces need for diabetes and
other medications
c No serious side effects
c Improves ASCVD risk factors
c Requires motivation
c Requires lifelong behavioral change
Variable, with potential for
very high efficacy; often
intermediate
Oral medications
Biguanides c Metformin c ↓ Hepatic glucose production
c Multiple other non-insulin-
mediated mechanisms
c Extensive experience
c No hypoglycemia
c Inexpensive
c GI symptoms
c Vitamin B12 deficiency
c Use with caution or dose adjustment
forCKDstage3B(eGFR30–44mLmin21
[1.73 m]22
)
c Lactic acidosis (rare)
High
SGLT2 inhibitors c Canagliflozin
c Dapagliflozin
c Empagliflozin
c Ertugliflozin
c Blocks glucose reabsorption
by the kidney, increasing
glucosuria
c ? Other tubulo-glomerular
effects
c No hypoglycemia
c ↓ Weight
c ↓ Blood pressure
c Effective at all stages of T2DM
with preserved glomerular function
c ↓ MACE, HF, CKD with some
agents (see text)
c Genital infections
c UTI
c Polyuria
c Volume depletion/hypotension/
dizziness
c ↑ LDL-C
c ↑ Creatinine (transient)
c Dose adjustment/avoidance for renal
disease
c ↑ Risk for amputation (canagliflozin)
c ↑ Risk for fracture (canagliflozin)
Intermediate–high
(dependent on GFR)
Continued on p. 2682
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2. Table 2—Continued
Class
Medications/therapies
in class Primary physiological action(s) Advantages Disadvantages/adverse effects Efficacy
c ↑ Risk for DKA (rare)
c Fournier’s gangrene (rare)
c Expensive
DPP-4 inhibitors c Sitagliptin
c Vildagliptina
c Saxagliptin
c Linagliptin
c Alogliptin
c Glucose dependent:
↑ Insulin secretion
↓ Glucagon secretion
c No hypoglycemia
c Weight neutral
c Well tolerated
c Rare urticaria/angioedema
c ↑ HF hospitalization (saxagliptin)
c Dose adjustment/avoidance for renal
disease depending on agent
c ? Pancreatitis
c ? Arthralgia
c ? Bullous pemphigoid
c Expensive (U.S.); variable in Europe
Intermediate
Sulfonylureas c Glibenclamide/glyburide
c Glipizide
c Gliclazidea
c Glimepiride
c ↑ Insulin secretion c Extensive experience
c ↓ Microvascular risk (UKPDS)
c Inexpensive
c Hypoglycemia
c ↑ Weight
c Uncertain cardiovascular safety
c Dose adjustment/avoidance for renal
disease
c High rate of secondary failure
High
TZDs c Pioglitazone
c Rosiglitazoneb
c ↑ Insulin sensitivity c Low risk for hypoglycemia
c Durability
c ↑ HDL-C
c ↓ Triacylglycerols (pioglitazone)
c ↓ ASCVD events (pioglitazone: in a
poststrokeinsulin-resistantpopulationand
as secondary end point in a high-risk-of-
CVD diabetes population)
c Lower cost
c ↑ Weight
c Edema/heart failure
c Bone loss
c ↑ Bone fractures
c ↑ LDL-C (rosiglitazone)
c ? Bladder cancer
c ? Macular edema
High
Meglitinides (Glinides) c Repaglinide
c Nateglinide
c ↑ Insulin secretion c ↓ Postprandial glucose excursions
c Dosing flexibility
c Safe in advanced renal disease with
cautious dosing (especially repaglinide)
c Lower cost
c Hypoglycemia
c ↑ Weight
c Uncertain cardiovascular safety
c Frequent dosing schedule
Intermediate–high
a-Glucosidase inhibitors c Acarbose
c Miglitol
c Slows carbohydrate
digestion/absorption
c Low risk for hypoglycemia
c ↓ Postprandial glucose excursions
c Nonsystemic mechanism of action
c Cardiovascular safety
c Lower cost
c Frequent GI side effects
c Frequent dosing schedule
c Dose adjustment/avoidance for renal
disease
Low–intermediate
Bile acid sequestrants c Colesevelamb
c ? ↓ Hepatic glucose
production
c ? ↑ Incretin levels
c No hypoglycemia
c ↓ LDL-C
c Constipation
c ↑ Triacylglycerols
c May ↓ absorption of other
medications
c Intermediate expense
Low–intermediate
Continued on p. 2683
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3. Table 2—Continued
Class
Medications/therapies
in class Primary physiological action(s) Advantages Disadvantages/adverse effects Efficacy
Dopamine-2 agonists c Quick-release
bromocriptineb
c Modulates hypothalamic
regulation of metabolism
c ↑ Insulin sensitivity
c No hypoglycemia
c ? ↓ ASCVD events
c Headache/dizziness/syncope
c Nausea
c Fatigue
c Rhinitis
c High cost
Low–intermediate
Injectable medications
Insulins
Long acting (basal) c Degludec (U100, U200)
c Detemir
c Glargine (U100, U300)
c Activates insulin receptor
c ↑ Glucose disposal
c ↓ Glucose production
c Nearly universal response
c Theoretically unlimited efficacy
c Once-daily injection
c Hypoglycemia
c Weight gain
c Training requirements
c Frequentdoseadjustmentforoptimal
efficacy
c High cost
Very high
Intermediate acting
(basal)
c Human NPH c Activates insulin receptor
c ↑ Glucose disposal
c ↓ Glucose production
c Nearly universal response
c Theoretically unlimited efficacy
c Less expensive than analogs
c Hypoglycemia
c Weight gain
c Training requirements
c Often given twice daily
c Frequent dose adjustment for optimal
efficacy
Very high
Rapid acting c Aspart (conventional and
fast acting)
c Lispro (U100, U200)
c Glulisine
c Activates insulin receptor
c ↑ Glucose disposal
c ↓ Glucose production
c Nearly universal response
c Theoretically unlimited efficacy
c ↓ Postprandial glucose
c Hypoglycemia
c Weight gain
c Training requirements
c May require multiple daily injections
c Frequent dose adjustment for optimal
efficacy
c High cost
Very high
Inhaled rapid acting c Human insulin inhalation
powderb
c Activates insulin receptor
c ↑ Glucose disposal
c ↓ Glucose production
c Nearly universal response
c ↓ Postprandial glucose
c More rapid onset and shorter duration
than rapid-acting analogs
c Spirometry (FEV1) required before
initiating, after 6 months, and
annually
c Contraindicated in chronic lung
disease
c Not recommended in smokers
c Hypoglycemia
c Weight gain
c Training requirements
c May require multiple inhalations daily
High
Continued on p. 2684
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4. Table 2—Continued
Class
Medications/therapies
in class Primary physiological action(s) Advantages Disadvantages/adverse effects Efficacy
c Frequent dose adjustment for optimal
efficacy; limited options in dosing
interval
c High cost
c Respiratory side effects (e.g.,
bronchospasm, cough, decline in
FEV1)
Short acting c Human regular (U100,
U500)
c Activates insulin receptor
c ↑ Glucose disposal
c ↓ Glucose production
c Nearly universal response
c Theoretically unlimited efficacy
c ↓ Postprandial glucose
c Less expensive than analogs
c Hypoglycemia
c Weight gain
c Training requirements
c Frequent dose adjustment for optimal
efficacy
c May require multiple daily injections
Very high
Premixed c Many c Activates insulin receptor
c ↑ Glucose disposal
c ↓ Glucose production
c Nearly universal response
c Theoretically unlimited efficacy
c Fewer injections than basal/bolus
before every meal
c Recombinant human analogs
are less expensive
c Hypoglycemia
c Weight gain
c Training requirements
c Frequent dose adjustment for optimal
efficacy
c High cost (except human insulin
premix)
c Can lead to obligate eating
Very high
GLP-1 RA
Shorter acting c Exenatide
c Lixisenatide
c Glucose dependent:
↑ Insulin secretion
↓ Glucagon secretion
c Slows gastric emptying
c ↑ Satiety
c No hypoglycemia as monotherapy
c ↓ Weight
c Excellent postprandial glucose
efficacy for meals after injections
c Improves cardiovascular risk
factors
c Frequent GI side effects that may be
transient
c Modestly ↑ heart rate
c Training requirements
c Dose adjustment/avoidance in renal
disease
c Acute pancreatitis (rare/uncertain)
c Very high cost
Intermediate–high
Longer acting c Dulaglutide
c Exenatide extended-
release
c Liraglutide
c Semaglutide
c Glucose dependent:
↑ Insulin secretion
↓ Glucagon secretion
c ↑ Satiety
c No hypoglycemia as monotherapy
c ↓ Weight
c ↓ Postprandial glucose excursions
c Improves cardiovascular risk factors
c ↓ MACE with some agents (see text)
c ↓ Albuminuria with some agents
(see text)
c GI side effects, including gallbladder
disease
c Greater ↑ heart rate
c Training requirements
c Dose adjustment/avoidance for some
agents in renal disease
c Acute pancreatitis (rare/uncertain)
High–very high
Continued on p. 2685
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5. Table 2—Continued
Class
Medications/therapies
in class Primary physiological action(s) Advantages Disadvantages/adverse effects Efficacy
c Greater lowering of fasting
glucose vs. short-acting preparations
c Once-weekly dosing (except
liraglutide, which is daily)
c C-cell hyperplasia/medullary thyroid
tumors (rare/uncertain; observed in
animals only)
c Very high cost
Other injectables
Amylin mimetics c Pramlintideb
c ↓ Glucagon secretion
c Slows gastric emptying
c ↑ Satiety
c ↓ Postprandial glucose excursions
c ↓ Weight
c Hypoglycemia
c Frequent dosing schedule
c Training requirements
c Frequent GI side effects
c Very high cost
Intermediate
Fixed-dose
combinationofGLP-1
RA and basal insulin
analogs
c Liraglutide/degludec
c Lixisenatide/glargine
c Combined activities of
components
c Enhanced glycemic efficacy vs. components
c Reduced adverse effects (e.g., GI,
hypoglycemia)
vs. components
c Less weight loss than GLP-1 receptor
agonist alone
c Very high cost
Very high
Weight loss medications c Lorcaserinb
c Naltrexone/bupropion
c Orlistat
c Phentermine/
topiramateb
c Liraglutide 3 mg
c Reduced appetite
c Fat malabsorption (orlistat)
c Mean 3–9 kg weight loss vs. placebo c High discontinuation rates from side
effects
c ,50% achieve $5% weight loss
c Drug-specific side effects
c Limited durability
c High cost
Intermediate
Metabolic surgery c VSG
c RYGB
c Adjustable gastric band
c BPD
c Restriction of food intake (all)
c Malabsorption (RYGB, BPD)
c Changes in hormonal and
possibly neuronal signaling
(VSG, RYGB, BPD)
c Sustained weight reduction
c ↑ Rate of remission of diabetes
c ↓ Number of diabetes drugs
c ↓ Blood pressure
c Improved lipid metabolism
c High initial cost
c ↑ Risk for early and late surgical
complications
c ↑ Risk for reoperation
c ↑ Risk for dumping syndrome
c ↑ Nutrient and vitamin malabsorption
c ↑ Risk for new-onset depression
c ↑ Risk for new-onset opioid use
c ↑ Risk for gastroduodenal ulcer
c ↑ Risk for hypoglycemia
c ↑ Risk for alcohol use disorder
Very high
More details available in ADA’s Standards of Medical Care in Diabetesd2018 (3). Glucose-lowering efficacy of drugs by change in HbA1c: .22 mmol/mol (2%) very high, 11–22 mmol/mol (1–2%)
high, 6–11 mmol/mol (0.5–1.5%) intermediate, ,6 mmol/mol (0.5%) low. a
Not licensed in the U.S. for type 2 diabetes. b
Not licensed in Europe for type 2 diabetes. BPD, biliopancreatic diversion;
DKA, diabetic ketoacidosis; FEV1, forced expiratory volume in 1 s on pulmonary function testing; GI, gastrointestinal; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HDL-C, HDL-cholesterol; LDL-C,
LDL-cholesterol; RYGB, Roux-en-Y gastric bypass; VSG, vertical sleeve gastroplasty; T2DM, type 2 diabetes mellitus; UTI, urinary tract infection.
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