Alpha glucosidase inhibitors such as acarbose inhibit the ability of alpha glucosidase to convert nonabsorbable dietary starch and sucrose into absorbable glucose, which results in slower glucose absorption and reduced postprandial glucose levels^1-4.

Metformin is an oral biguanide antihyperglycemic agent that improves glycemic control by decreasing hepatic glucose production and intestinal glucose absorption as well as improving insulin sensitivity through increased peripheral glucose uptake and utilization^1,2,5-8.

The bile acid sequestrant, colesevelam, is FDA-approved for use to manage primary hyperlipidemia as well as type 2 diabetes as an adjunct to diet and exercise. The mechanism by which colesevelam lowers hemoglobin A1c (HbA1c) and improves glycemic control is unknown^1,2,9.

DPP-IV inhibitors reduce inactivation of incretin hormones and improve glycemic control in type 2 diabetic patients without significant weight gain. The incretin hormones, glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic peptide (GIP), have been identified as important factors in glucose homeostasis. Released from the gut postprandially, GLP-1 and GIP stimulate insulin secretion from pancreatic beta cells in response to normal or elevated blood glucose concentrations. GLP-1 also lowers glucagon excretion from pancreatic beta cells, which results in reduced hepatic glucose production, reduced appetite, slowed gastric emptying, and improved β-cell function^1,2,10-13 .

Bromocriptine, a dopamine agonist, is FDA-approved as Cycloset® to manage glycemic control in type 2 diabetes as an adjunct to diet and exercise through a currently undetermined mechanism^1,2,14 .

Although GLP-1 agonists are primarily administered as a subcutaneous injection, semaglutide (Rybelsus®) received FDA approval as the first oral GLP-1 agonist used for the management of type 2 diabetes. Of note, semaglutide has not demonstrated a reduction in adverse cardiovascular outcomes while several injectable formulations have^1,2,15,16.

Meglitinides, such as nateglinide and repaglinide, stimulate insulin secretion by inhibiting ATP-sensitive potassium channels in pancreatic beta-cells^1,2,17,18.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors work by inhibiting SGLT2 transporters in the proximal renal tubule and reduce reabsorption of filtered glucose causing increased glucose excretion and lower serum glucose concentrations. Recent studies regarding these medications have provided the support for the addition of new indications. Canagliflozin, empagliflozin, and dapagliflozin have demonstrated a reduction of risk of cardiovascular death and reduction of risk of hospitalization for heart failure in patients with type 2 diabetes. Additionally, canagliflozin and dapagliflozin also have a new indication for the reduction of major cardiovascular events, and reduction of risk of sustained eGFR decline and end-stage renal disease in patients with type 2 diabetes. Empagliflozin and dapagliflozin have additional FDA approvals for patients without type 2 diabetes mellitus^1,2,19-22 .

Oral sulfonylureas reduce blood glucose by stimulating insulin from pancreatic beta-cells as well as increasing responsiveness in insulin-sensitive tissues^1,2,23-27.

Thiazolidinediones are potent agonists of peroxisome proliferator-activated receptor-gamma (PPAR-gamma), receptors important for insulin action which are in adipose tissue, the liver, and skeletal muscle. Activation of these receptors affects the transcription of genes responsible for control of glucose and lipid metabolism. These agents, in the presence of insulin, decrease insulin resistance in the liver and at peripheral sites and improve insulin-dependent glucose disposal and reduce hepatic glucose output^1,2,28,29.

Thiazolidinediones have been associated with an increased risk of congestive heart failure most likely due to a greater incidence of fluid retention/edema associated with this drug class. Patients should be closely monitored for signs and symptoms of CHF, and thiazolidinedione dosages reduced or discontinued should symptoms develop. Thiazolidinediones are contraindicated for use in NYHA Class III or IV heart failure and are not recommended in patients with symptomatic heart failure^1,2,28,29.

Female patients treated with thiazolidinediones may be at increased risk for developing fractures. These agents have been shown to stimulate formation of more adipocytes rather than osteoblasts in bone. Thiazolidinediones may also decrease hip and femoral neck bone mineral density in older diabetic patients. Fractures currently reported with thiazolidinedione use have been limited to the humerus, hand, and foot in female patients only. Further assessment of thiazolidinedione adverse skeletal effects is necessary to determine the risk-benefit ratio of these agents in diabetic patients. Female patients at higher fracture risk should be considered for bone mineral density assessment and bone strengthening therapies (e.g., calcium, vitamin D, bisphosphonates) prior to therapy initiation with thiazolidinediones^1,2,28,29.

Maximum recommended daily doses for available oral antidiabetic agents, both as monotherapy and as combination therapy, are summarized in Tables 1 and 2. Prescribed dosages exceeding these recommendations will be reviewed.

Table 1. Oral Antidiabetic Agents- Monotherapy: Alpha-Glucosidase Inhibitors (AGIs) Maximum Recommended Adult Daily Dosages^1-4

Drug Name	Dosage Form/Strength	Therapeutic Indications	Maximum Recommended Dosage
acarbose (generics)	25 mg, 50 mg, 100 mg tablets	type 2 diabetes	patients less than or equal to 60 kg: 150 mg/day, in three divided doses patients greater than 60 kg: 300 mg/day, in three divided doses
miglitol (generics)	25 mg, 50 mg, 100 mg tablets	type 2 diabetes	300 mg/day, in three divided doses

Table 2. Oral Antidiabetic Agents- Monotherapy: Biguanides Maximum Recommended Adult Daily Dosages^1,2,5-8

Drug Name	Dosage Form/Strength	Therapeutic Indications	Maximum Recommended Dosage
metformin (generics)	500 mg, 850 mg, 1000 mg immediate-release tablets	type 2 diabetes	2550 mg/day
metformin (Fortamet®, Glumetza®, various generics)	500 mg, 750 mg, 1000 mg extended-release tablets	type 2 diabetes	2000 mg/day (2500 mg/day Fortamet®)
metformin (Riomet®, generics)	500 mg/5 mL oral solution	type 2 diabetes	2550 mg/day

Table 3. Oral Antidiabetic Agents- Monotherapy: Bile Acid Sequestrants Maximum Recommended Adult Daily Dosages^1,2,9

Drug Name	Dosage Form/Strength	Therapeutic Indication	Maximum Recommended Dosage
colesevelam (Welchol®, generic))	625 mg tablets	type 2 diabetes	3.75 g/day, in single or two divided doses
colesevelam (Welchol®, generic))	3.75 g powder packet for oral suspension#	type 2 diabetes	3.75 g/day as single dose

Legend:

• # dissolve in 4-8 ounces of water, fruit juice or diet soda and administer with a meal

Table 4. Oral Antidiabetic Agents- Monotherapy: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors Maximum Recommended Adult Daily Dosages^1,2,10-13

Drug Name	Dosage Form/Strength	Therapeutic Indication	Maximum Recommended Dosage
alogliptin (Nesina®, generics)	6.25 mg, 12.5 mg, 25 mg tablets	type 2 diabetes	25 mg/day
linagliptin (Tradjenta®)	5 mg	type 2 diabetes	5 mg/day
saxagliptin (Onglyza®)	2.5 mg, 5 mg tablets	type 2 diabetes	5 mg/day
sitagliptin (Januvia®)	25 mg, 50 mg, 100 mg tablets	type 2 diabetes	100 mg/day

Table 5. Oral Antidiabetic Agents- Monotherapy: Dopamine Agonists Maximum Recommended Adult Daily Dosages^1,2,14

Drug Name	Dosage Form/Strength	Treatment Indication	Maximum Recommended Dosage
bromocriptine (Cycloset®)	0.8 mg tablets	type 2 diabetes mellitus	4.8 mg/day

Table 6. Oral Antidiabetic Agents- Monotherapy: Glucagon-Like Peptide-1 (GLP-1) Agonist Maximum Recommended Adult Daily Dosages^1,2,15

Drug Name	Dosage Form/Strength	Treatment Indication	Maximum Recommended Dosage
semaglutide (Rybelsus®)	3 mg, 7 mg, 14 mg tablets	type 2 diabetes	14 mg/day

Table 7. Oral Antidiabetic Agents- Monotherapy: Meglitinides Maximum Recommended Adult Daily Dosages^1,2,17,18

Drug Name	Dosage Form/Strength	Treatment Indication	Maximum Recommended Dosage
nateglinide (generics)	60 mg, 120 mg tablets	type 2 diabetes	360 mg/day, in three divided doses
repaglinide (generics)	0.5 mg, 1 mg, 2 mg tablets	type 2 diabetes	16 mg/day (in divided doses before meals, up to 4 times daily depending on meal number)

Table 8. Oral Antidiabetic Agents- Monotherapy: Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors Maximum Recommended Adult Daily Dosages^1,2,19-22

Drug Name	Dosage Form/Strength	Treatment Indication	Maximum Recommended Dosage
Canagliflozin (Invokana®)	100 mg, 300 mg tablets	type 2 diabetes*	300 mg/day
dapagliflozin (Farxiga®)	5 mg, 10 mg tablets	type 2 diabetes!	10 mg/day
empagliflozin (Jardiance®)	10 mg, 25 mg tablets	type 2 diabetes#	25 mg/day
ertugliflozin (Steglatro®)	5 mg, 15 mg tablets	type 2 diabetes	15 mg/day

Legend:

• * FDA approved to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease; to reduce the risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria
• ! FDA approved to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors, reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure with reduced ejection fraction (NYHA class II-IV), and to reduce the risk of sustained eGFR decline, end stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression
• # FDA approved to reduce the risk of cardiovascular death and hospitalization due to heart failure in adults with heart failure, and to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease 

Table 9. Oral Antidiabetic Agents- Monotherapy: Sulfonylureas Maximum Recommended Adult Daily Dosages^1,2,23-27

Drug Name	Dosage Form/Strength	Treatment Indication	Maximum Recommended Dosage
glimepiride (Amaryl®, generics)	1 mg, 2 mg, 4 mg tablets	type 2 diabetes	8 mg/day
glipizide (generics)	5 mg, 10 mg immediate-release tablets	type 2 diabetes	40 mg/day
glipizide (Glucotrol XL®, generics)	2.5 mg, 5 mg, 10 mg extended-release tablets	type 2 diabetes	20 mg/day
glyburide (generics)	1.25 mg, 2.5 mg, 5 mg non-micronized tablets	type 2 diabetes	20 mg/day
glyburide (Glynase®, generics)	1.5 mg, 3 mg, 6 mg micronized tablets	type 2 diabetes	12 mg/day

Table 10. Oral Antidiabetic Agents- Monotherapy: Thiazolidinediones (TZDs) Maximum Recommended Adult Daily Dosages^1,2,28,29

Drug Name	Dosage Form/Strength	Treatment Indication	Maximum Recommended Dosage
pioglitazone (Actos®, generics)	15 mg, 30 mg, 45 mg tablets	type 2 diabetes	45 mg/day
rosiglitazone (Avandia®)	2 mg, 4 mg tablets	Type 2 diabetes	8 mg/day in single or two divided doses

Table 11. Oral Antidiabetic Agents- Combination Therapy: Maximum Recommended Adult Daily Dosages^1,2,30-49

Drug Name	Dosage Form/Strength	Treatment Indication	Maximum Recommended Dosage
alogliptin/metformin (Kazano®, generics)	12.5 mg/500 mg, 12.5 mg/1000 mg tablets	type 2 diabetes	25 mg/2000 mg/day
alogliptin/pioglitazone (Oseni®, generics)	12.5 mg/15 mg, 12.5 mg/30 mg, 12.5 mg/45 mg, 25 mg/15 mg, 25 mg/30 mg, 25 mg/45 mg tablets	type 2 diabetes	25 mg/45 mg/day
canagliflozin/metformin (Invokamet®)	50 mg/500 mg, 50 mg/1000 mg, 150 mg/500 mg, 150 mg/1000 mg tablets	type 2 diabetes*	300 mg/2000 mg/day in two divided doses
canagliflozin/metformin (Invokamet® XR)	50 mg/500 mg, 50 mg/1000 mg, 150 mg/500 mg, 150 mg/1000 mg extended-release tablets	type 2 diabetes*	300 mg/2000 mg/day once daily
dapagliflozin/ metformin (Xigduo® XR)	2.5 mg/1000 mg, 5 mg/500 mg, 5 mg/1000 mg, 10 mg/500 mg, 10 mg/1000 mg tablets	type 2 diabetes!	10 mg/2000 mg/day once daily
dapagliflozin/saxagliptin (Qtern®)	5 mg/ 5 mg, 10 mg/5 mg tablets	type 2 diabetes	10 mg/5 mg/day once daily
empagliflozin/ linagliptin (Glyxambi®)	10 mg/5 mg, 25 mg/5 mg tablets	type 2 diabetes^	25 mg/5 mg/day
empagliflozin/metformin (Synjardy®)	5 mg/500 mg, 5 mg/1000 mg, 12.5 mg/500 mg, 12.5 mg/1000 mg tablets	type 2 diabetes^	25 mg/2000 mg/day in two divided doses
empagliflozin/ metformin (Synjardy® XR)	5 mg/ 1000 mg, 10 mg/1000 mg, 12.5 mg/1000 mg, 25 mg/1000 mg extended-release tablets	type 2 diabetes^	25 mg/2000 mg/day once daily
empagliflozin/linagliptin/metformin (Trijardy® XR)	5 mg/2.5 mg/1000 mg, 10 mg/5 mg/1000 mg, 12.5 mg/2.5 mg/1000mg, 25 mg/5 mg/1000 mg extended-release tablets	type 2 diabetes^	25 mg/ 5 mg/ 2000 mg daily
ertugliflozin/metformin (Segluromet®)	2.5 mg/500 mg, 2.5 mg/1000 mg, 7.5 mg/500 mg, 7.5 mg/1000 mg tablets	type 2 diabetes	15 mg/2000 mg/day in two divided doses
ertugliflozin/sitagliptin (Steglujan®)	5 mg/100 mg, 15 mg/100 mg tablets	type 2 diabetes	15 mg/100 mg/day once daily
glipizide/ metformin (generics)	2.5 mg/250 mg, 2.5 mg/500 mg, 5 mg/500 mg	type 2 diabetes	Patients with inadequate glycemic control on diet/exercise alone: 10 mg/2000 mg/day Patients with inadequate glycemic control on sulfonylurea and/or metformin: 20 mg/2000 mg/day
glyburide/metformin (generics)	1.25 mg/250 mg, 2.5 mg/500 mg, 5 mg/500 mg tablets	type 2 diabetes	Patients with inadequate glycemic control on diet/exercise alone: 10 mg/2000 mg/day Patients with inadequate glycemic control on sulfonylurea and/or metformin: 20 mg/2000 mg/day
linagliptin/ metformin (Jentadueto®)	2.5 mg/500 mg, 2.5 mg/850 mg, 2.5 mg/1000 mg immediate-release tablets	type 2 diabetes	5 mg/2000 mg/day in two divided doses
linagliptin/metformin (Jentadueto® XR)	2.5 mg/1000 mg, 5 mg/1000 mg extended-release tablets	type 2 diabetes	5 mg/2000 mg/day once daily
pioglitazone/glimepiride (Duetact®, generics)	30 mg/2 mg, 30 mg/4 mg tablets	type 2 diabetes	30 mg/4 mg once daily
pioglitazone/metformin (ActoPlus Met®, generics)	15 mg/500 mg, 15 mg/850 mg immediate-release tablets	type 2 diabetes	45 mg/2550 mg/day
saxagliptin/metformin (Kombiglyze® XR)	5 mg/500 mg, 5 mg/1000 mg, 2.5 mg/1000 mg extended-release tablets	type 2 diabetes	5 mg/2000 mg/day
sitagliptin/ metformin (Janumet®)	50 mg/500 mg, 50 mg/1000 mg immediate-release tablets	type 2 diabetes	100 mg/2000 mg/day in two divided doses
sitagliptin/ metformin (Janumet XR®)	50 mg/500 mg, 50 mg/1000 mg, 100 mg/1000 mg extended-release tablets	type 2 diabetes	100 mg/2000 mg/day once daily

Legend:

• * FDA approved to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease; to reduce the risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria
• ! FDA approved to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors, reduce the risk of cardiovascular death and hospitalization due to heart failure in adults with heart failure with reduced ejection fraction (NYHA class II-IV), and to reduce the risk of sustained eGFR decline, end stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression
• ^ Empagliflozin is FDA approved to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease

Risperidone has been FDA-approved to manage symptoms of irritability in autistic children greater than 5 years of age and adolescents, and has recently gained FDA-approved indications for bipolar mania in children and adolescents 10 to 17 years of age and schizophrenia in adolescents 13 to 17 years of age. Aripiprazole has received recent FDA approval for treating Tourette’s disorder in pediatric patients 6 to 18 years of age, and is also FDA-approved for managing schizophrenia in adolescents 13 to 17 years of age, bipolar disorder with or without psychotic features in children 10 to 17 years of age, and irritability associated with autistic disorder in children 6 to 17 years of age. Olanzapine has been granted FDA approval for bipolar disorder and schizophrenia in adolescents 13 years of age and older. Quetiapine is FDA approved for acute treatment of bipolar disorder mania episodes in children and adolescents 10 to 17 years of age and schizophrenia management in adolescents 13 to 17 years of age. Paliperidone is approved FDA for the management of schizophrenia in adolescents 12 to 17 years of age. Lurasidone is approved for the management of depressed phase bipolar disorder in children 10 to 17 years of age, and it is approved for the management of schizophrenia in patients 13 to 17 years of age. Brexpiprazole, cariprazine, clozapine, iloperidone, Lumateperone, ziprasidone, and aripiprazole tablets with sensors (Abilify MyCite®) are not recommended for use in pediatric patients as safety and efficacy have not been established in this patient population. Additionally, pimavanserin is not approved for use in pediatric patients as Parkinson’s disease is typically not observed in pediatric patients, and safety and efficacy data are not available for pimavanserin in the pediatric population ^1-25.

Atypical antipsychotic pediatric dosages are summarized in Table 3. An additional column reflecting literature-based dosing included in the Texas Health and Human Services Psychotropic Medication Utilization Parameters for Children and Youth in Texas Public Behavioral Health (6th Version) is included in Tables 3 ^{1-21, 23, 26} and 4 ²⁶.

The olanzapine/fluoxetine combination has been approved for use in pediatric patients 10-17 years of age with depression associated with BD ^{1-4, 22}. Recommended pediatric dosages are summarized in Table 4 ^{1-4, 22, 26}.