Overview

Diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, type 2

• Caused by: 
  • Peripheral insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance: cell insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin receptors do not respond appropriately to insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin
  • Beta-cell dysfunction: long-term ↑ in insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin demand → defective insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin secretion
• Results in hyperglycemia
• Pharmacologic management can target:
  • Insulin release
  • Insulin resistance
  • Glucagon release
  • Gluconeogenesis
  • Glucose uptake

Classification

Hyperglycemic medications can be classified on the basis of their mechanism of action: 

Insulinotropic drugs: ↑ insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin secretion

• Sulfonylureas
• Meglitinides
• Glucagon-like peptide-1 (GLP-1) analogs
• DPP-4 inhibitors

Non-insulinotropic drugs: do not affect insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin release 

• ↓ Insulin resistance:
  • Biguanides
  • Thiazolidinediones (TZDs)
• ↓ Glucose absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption/reabsorption:
  • Alpha-glucosidase inhibitors
  • Sodium–glucose transport protein 2 (SGLT2) inhibitors
• ↓ Gastric emptying and glucagon secretion: amylin analogs

Biguanides

Metformin is the only available medication in the biguanide drug class.

Pharmacodynamics Pharmacodynamics Pharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is "what the body does to the drug," whereas pharmacodynamics is "what the drug does to the body." Pharmacokinetics and Pharmacodynamics

• The mechanism of action for metformin is not well understood, but it appears to help in the management of type 2 diabetes by:
  • ↓ Gluconeogenesis in:
    • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver
    • Kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys
  • ↓ GI glucose absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption
  • ↓ Insulin resistance
  • ↑ Uptake of glucose by:
    • Muscle
    • Adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or "brite" adipose tissue, which is a transitional form. Adipose Tissue
• Physiologic effect:
  • ↓ Fasting and postprandial glucose
  • Weight stabilization or reduction
  • ↓ LDL 
  • ↑ HDL

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

• Absorption: oral
• Distribution:
  • Concentrates in:
    • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver
    • Kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys
    • GI tract
  • Negligible protein binding
• Excretion: by the kidneys (unmetabolized)

Indications

• Type 2 diabetes:
  • Drug of choice for most cases
  • Well tolerated
  • Low cost 
  • No risk of hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia with monotherapy
• Polycystic ovary syndrome (no longer 1st-line treatment)

Adverse effects

• GI effects (improves with dose reduction or discontinuation):
  • Metallic taste
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea 
  • Anorexia 
  • Nausea and vomiting
• Lactic acidosis:
  • Rare
  • Common in individuals with concurrent renal and hepatic disease
  • Due to impairment of lactic acid metabolism in hepatocytes → released in bloodstream
• Vitamin B₁₂ deficiency
  • Occurs during long-term therapy 
  • Due to ↓ GI absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption of vitamin B₁₂
  • Rarely results in megaloblastic anemia Megaloblastic anemia Megaloblastic anemia is a subset of macrocytic anemias that arises because of impaired nucleic acid synthesis in erythroid precursors. This impairment leads to ineffective RBC production and intramedullary hemolysis that is characterized by large cells with arrested nuclear maturation. The most common causes are vitamin B12 and folic acid deficiencies. Megaloblastic Anemia

Contraindications

• Severe renal disease
• History of lactic acidosis
• Severe hepatic dysfunction
• Diabetic ketoacidosis Diabetic ketoacidosis Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency. Hyperglycemic Crises
• Avoid use:
  • Surgery
  • Iodinated contrast agents 
  • Hypoperfusion states

Drug interactions

Drugs associated with increased metformin toxicity:

• Ethanol
• Iodinated contrast agents
• Topiramate

Thiazolidinediones

Medications in this class

• Pioglitazone
• Rosiglitazone

Pharmacodynamics Pharmacodynamics Pharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is "what the body does to the drug," whereas pharmacodynamics is "what the drug does to the body." Pharmacokinetics and Pharmacodynamics

• Work on:
  • Muscle
  • Adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or "brite" adipose tissue, which is a transitional form. Adipose Tissue
• Ligands of peroxisome proliferator–activated receptors (PPARs)
• Activation of PPARs → ↑ transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription of genes involved in: 
  • Lipid and glucose metabolism
  • Insulin signal transduction
  • Adipocyte and other tissue differentiation
• ↑ Insulin sensitivity → ↑ glucose uptake and utilization

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

• Absorption: 
  • Well absorbed orally
  • Delayed onset of action
• Distribution: highly protein-bound
• Metabolism: 
  • Extensive hepatic metabolism
  • Cytochrome P450 system
  • Pioglitazone has active metabolites.
• Excretion: 
  • Pioglitazone: mostly in feces
  • Rosiglitazone: mostly in urine

Indications

TZDs are used for the treatment of type 2 diabetes:

• Not generally used in initial therapy
• More often used as 2nd- or 3rd-line therapy
• Can be combined with other agents
• Pioglitazone is useful in individuals with concurrent nonalcoholic steatohepatitis (NASH).

Adverse effects

• Weight gain:
  • Adipocyte proliferation
  • Fluid retention
• ↑ Risk of congestive heart failure Congestive heart failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure and cardiovascular events (especially with rosiglitazone)
• Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones demineralization and ↑ fragility 
• Hepatotoxicity
• Possible ↑ bladder cancer risk (pioglitazone)

Contraindications

• Class III or IV congestive heart failure Congestive heart failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure
• Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver failure

Drug interactions

• ↑ Hypoglycemic effect:
  • Other antidiabetic medications
  • Androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens
  • Direct-acting antiviral agents
  • Antidepressants
• Fluid retention: 
  • Pregabalin
  • Insulin
• ↑ Risk of ischemic events:
  • Vasodilators
  • Insulin

Alpha-Glucosidase Inhibitors

Medications in this class

• Acarbose 
• Miglitol

Pharmacodynamics Pharmacodynamics Pharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is "what the body does to the drug," whereas pharmacodynamics is "what the drug does to the body." Pharmacokinetics and Pharmacodynamics

• Alpha glucosidases: 
  • Intestinal brush border enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes 
  • Convert carbohydrates Carbohydrates Carbohydrates are one of the 3 macronutrients, along with fats and proteins, serving as a source of energy to the body. These biomolecules store energy in the form of glycogen and starch, and play a role in defining the cellular structure (e.g., cellulose). Basics of Carbohydrates → monosaccharides 
  • Only monosaccharides can be transported from the gut lumen → bloodstream
• Competitive inhibition → ↓ carbohydrate digestion Digestion Digestion refers to the process of the mechanical and chemical breakdown of food into smaller particles, which can then be absorbed and utilized by the body. Digestion and Absorption in the proximal small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine → deferred to distal small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine
• Results in slowed glucose absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption → ↓ post-meal glycemic excursion

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

• Absorption:
  • Acarbose: most is not absorbed
  • Miglitol: completely absorbed
• Metabolism:
  • Acarbose: degraded in the intestine by bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview and digestive enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
  • Miglitol: none
• Excretion:
  • Acarbose: mostly in feces
  • Miglitol: mostly in urine

Indications

Alpha-glucosidase inhibitors are used to treat type 2 diabetes as either:

• Monotherapy (generally not 1st-line)
• Adjunctive therapy

Adverse effects

• GI discomfort (due to fermentation of undigested carbohydrates Carbohydrates Carbohydrates are one of the 3 macronutrients, along with fats and proteins, serving as a source of energy to the body. These biomolecules store energy in the form of glycogen and starch, and play a role in defining the cellular structure (e.g., cellulose). Basics of Carbohydrates in the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix):
  • Flatulence
  • Bloating
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
• ↑ Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes

Contraindications

• Renal impairment
• Hepatic impairment
• GI motility disease
• Predisposition to bowel obstruction
• Inflammatory bowel disease

Sodium–glucose transport protein 2 (SGLT2) Inhibitors

Medications in this class

• Dapagliflozin
• Empagliflozin 
• Canagliflozin 
• Ertugliflozin

Pharmacodynamics Pharmacodynamics Pharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is "what the body does to the drug," whereas pharmacodynamics is "what the drug does to the body." Pharmacokinetics and Pharmacodynamics

• SGLT2:
  • Located in the proximal tubule 
  • Responsible for glucose reabsorption
• Inhibition of SGLT2 → ↓ reabsorption of filtered glucose
• Result: ↑ urinary glucose excretion and ↓ blood glucose level

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

• Absorption: rapid oral absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption
• Distribution: protein-bound
• Metabolism:
  • Hepatic
  • Glucuronidation
  • Minimal cytochrome P450–mediated metabolism
• Excretion: in urine and feces

Indications

Sodium–glucose transport protein 2 inhibitors are used for the treatment of type 2 diabetes:

• Adjunctive therapy
• Not typically used as initial therapy
• Help with weight loss
• Potential morbidity and mortality benefit for individuals with cardiovascular and renal comorbidities

Adverse effects

• Glucosuria → ↑ risk of genitourinary tract infections
• Osmotic diuresis leads to:
  • Polyuria
  • Hypovolemia
  • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
  • AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury
• ↑ Risk of fractures
• ↑ Risk of diabetic ketoacidosis

Contraindications

• Severe renal impairment (less effective)
• Frequent urinary tract infections Urinary tract infections Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections
• Type 1 diabetes
• Diabetic ketoacidosis Diabetic ketoacidosis Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency. Hyperglycemic Crises

Amylin Analogs

Pramlintide is the only medication in the amylin analog class.

Pharmacodynamics Pharmacodynamics Pharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is "what the body does to the drug," whereas pharmacodynamics is "what the drug does to the body." Pharmacokinetics and Pharmacodynamics

• Amylin is usually cosecreted with insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin by beta cells in the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas.
• This secretion is deficient in type 1 diabetes and relatively deficient in type 2 diabetes.
• Analogs help with glucose control by:
  • Slowing gastric emptying and ↑ satiety → ↓ food intake
  • ↓ Postprandial glucagon secretion

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

• Absorption: given as a subcutaneous injection
• Metabolism:
  • Renal
  • Active metabolite
• Excretion: in urine

Indications

• Used in types 1 and 2 diabetes
• Individuals should be on prandial insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin.
• Administered immediately prior to meals

Adverse effects

• Nausea and vomiting
• Anorexia
• Hypoglycemia (usually in type 1 diabetes)

Contraindications

• Gastroparesis
• Hypoglycemia unawareness

Drug interactions

• ↑ Hypoglycemic effect with other antidiabetic medications
• May delay absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption of oral medications

Comparison of Antidiabetic Medications

The following table compares the different (noninsulin) type 2 diabetes mellitus medications:

The effects of diabetes medications on weight may be a factor in choosing therapy:

• Weight loss:
  • GLP-1 mimetics
  • SGLT2 inhibitors
• Weight neutral:
  • α-glucosidase inhibitors
  • DPP-4 inhibitors
• Weight gain:
  • Insulin
  • Sulfonylureas
  • Thiazolidinediones
  • Meglitinides