thyroid pharmacology, androgens and antiandrogens, diabetes mellitus, corticosteroids

Question 1

what is hypothyroidism? hyperthyroidism?

Answer 1

• Hypothyroidism - Low T4 & High TSH

* Hyperthyroidism - High T4 & Low TSH.

Question 2

hypothyroidism treatment?

Answer 2

o The treatment for all forms of hypothyroidism is replacement therapy with either T3 or T4.
o Synthetic Levothyroxine sodium salt (T4) is the form of choice for most cases.
o Note the administered T4 is converted to T3 in vivo.
o Liothyronine sodium (L-T3): It is faster-acting, has higher oral bioavailability, but has a shorter half-life and is more expensive.
o T3 is the active form but it is degraded rapidly.

Question 3

hyperthyroidism treatment?

Answer 3

o 1. Antithyroid agents: Inhibit the Synthesis of T3 & T4.
o 2. Iodide Salt: inhibits iodination of tyrosine & thyroid hormone release. Effective for a maximum of 2 weeks.
o 3. Iodinated Radiocontrast media: Suppresses the peripheral conversion of T4 to T3.
o 4. Radioactive iodine (RAI) therapy: 131I (radioiodine) ablation of thyroid tissue (The most popular method).
o 5. Surgery: Thyroidectomy - Surgical removal of the thyroid is occasionally used as a treatment.
o 6. Beta-blocker: As an adjunct to inhibit the hyper- sympathetic function of hyperthyroidism.

Question 4

antithyroid agents - thiourea drugs?

Answer 4

thyroid pharmacology -
• Propylthiouracil (PTU) & Methimazole
o Note: PTU (but not methimazole) also inhibits the conversion of T4 to T3 in peripheral tissues. XX
• Propylthiouracil (PTU) & Methimazole
• Indications:
• In GRAVE’s Disease (Hyperthyroidism], Thiourea drugs are used to induce remission or control symptoms prior to surgery or administration of radioactive iodine treatment.
• Since synthesis of thyroid hormone rather than its release is inhibited, the onset of activity of these drugs is usually slow, often requiring 2 weeks for the full effect to manifest. So, if you give KI, it will block the release of T3 and T4.
• Potassium Iodide (KI) duration of effect is short lived [2 weeks]. By that time PTU or Methimazole treatment would have reduced T3/T4 production.

• Adverse effect:
o Skin rash (common) urticarial papular rash
o Severe immunological reactions such as leukopenia, agranulocytosis, or vasculitis.
o these effects are usually reversible upon withdrawal of the drugs.
o PTU & Methimazole must be used cautiously during pregnancy and in nursing women.
o since both agents can cross the placenta and enter breast milk. (methimazole > PTU).
o Q: What might happen if we treated a pregnant woman aggressively with a thiourea - PTU?
o (risk of developing cretinism in the developing fetus).

Question 5

iodide salt treatment for hyperthyroidism

Answer 5

• Iodide Salt:
o It inhibits iodination of tyrosine & thyroid hormone release (acts for a short term 10 days to 2 weeks days) decreases vascularity, helpful in reducing the size.
o Usual forms - Lugol’s solution
o (iodine and potassium iodide).
o Mechanisms:
o - inhibit iodination of tyrosine & thyroid hormone release.
o - decrease the size and vascularity of the hyperplastic thyroid gland.
o -onset of action occurs rapidly within 2-7 days. Shorter duration
o Potassium iodide solution: Short term – Lugol’s Iodine
o the effects are transient - because the thyroid gland “escapes” from the iodide block after several weeks of treatment.
o Indication:
o - used on a short-term basis to treat patients with “thyroid storm”.
o - prepare patients for thyroid surgery.
o - Inhibit the release of thyroid hormones following
o radioactive Iodine (RAI) therapy.
o Adverse effect:
o - skin rashes & other hypersensitivity reactions

Question 6

Iodinated Radio-contrast media

Answer 6

o Certain iodinated radiocontrast media (e.g. Ipodate effectively suppress the conversion of T4 to T3 via 5’-deiodinase in the liver, kidney, and other peripheral tissues.
o Inhibition of hormone release from the thyroid may also play a part.
o Ipodate has proved to be very useful in rapidly reducing T3 concentrations in thyrotoxicosis.

Question 7

radioactive iodine RAI (131I)

Answer 7

o 131I is used for thyroid ablation, its half life is 8 days.
o 123I is used for thyroid function test short half life-13 hr.
o Radioactive Iodine is taken up and concentrated in the thyroid gland – emits g and b radiation destroying thyroid tissue without endangering other tissues.
o Unlike thiourea drugs and iodide salts, an effective dose of [131I] can produce a permanent cure of thyrotoxicosis without surgery.
o After RAI treatment, iodide salts are used to inhibit thyroid hormone release.
o [131I] should NOT be used in pregnant or nursing women as it may affect the fetus/newborn.

Question 8

beta blockers thyroid stuff

Answer 8

o β -adrenergic receptor antagonists such as Propranolol are particularly useful in controlling tachycardia and other cardiac abnormalities of severe acute Thyrotoxicosis (thyroid storm).
o Thyroid hormone and the sympathetic nervous system act synergistically on cardiovascular function, so increased levels of thyroid hormone causes tachycardia & arrhythmia. Therefore, non-selective b- blockers such as propranolol are always given in thyroid storm and severe hyperthyroidism to control enhanced sympathetic drive and tachycardia.

Question 9

synthetic androgens, preparations of testosterone

Answer 9

androgens and antiands -
17α methyl testosterone (oral or sublingual preparations are availabled)

• Testosterone propionate (androgenic ester) parenteral - s.c or i.m. route.
• Stanozolol (synthetic anabolic steroid derived from Dihydrotestosterone with less androgenic activity and more anabolic activity).
Actions:
1) Androgenic action:
• Maturation of testis, prostate, seminal vesicle, scrotum and penis.
• Skin: Increases the sebaceous gland secretion, thickening of skin, acne. Increases the body hair distribution- [axillary, pubic and beard - male type hair development]
2) Anabolic action: consider giving in cachectic patients, prolonged illness.
• Increase in muscle mass.
• Increases in protein anabolism.

Question 10

Hypogonadism

Answer 10

Testosterone replacement stimulates the anterior pituitary to increase gonadotropins and promotes secondary sex characteristics.
• In osteoporosis.
• In trauma: To decrease protein loss. To promote + ve nitrogen balance.
• In Post operative Convalescence.
• In the management of intractable anaemia.

Adverse effects:
• Acne, Prostatic hyperplasia and hypertrophy.
• Behavioural changes, Aggressiveness, Psychotic symptoms.
• Hepatic Dysfunction- Cholestatic Jaundice is encountered (esp. with 17α methyl substituted synthetic steroids - anabolic, androgens & progestins).

Question 11

control of androgen secretion and sites of action of antiandrogens

Answer 11

Leuprolide, a synthetic Gn-RH analogue, agonist, Decreases FSH/LH production. After an initial flare, it decreases male gonadal function.**
Abarelix – antagonist does not have the initial flare. Both are useful in the management of prostate cancer by Decreasing LH-dependent testosterone production. Testosterone is essential for the prostate hypertrophy and hyperplasia.**
Therapeutic uses: To treat Prostate Cancer (Leuprolide/Abarelix)

Question 12

finasteride

Answer 12

antiandrogen - • It is a Steroid.
• It inhibits the conversion of testosterone to Dihydrotestosterone(DHT),
• DHT: an active metabolite that mediates the androgenic action of Testosterone by inhibiting 5α reductase enzyme. DHT is the active androgen.
• Finasteride is the 5α Reductase Inhibitor.**
Use: Prostate Cancer and Hirsutism (Finasteride)

Question 13

spironolactone

Answer 13

androgens and antiandr.
Note: Spironolactone, a steroid antagonist that decreases the biosynthesis of Testosterone in the Leydig cells of testis besides serving as a major Aldosterone Competitive Antagonist.
It also blocks the dihydrotestosterone mediated androgenic responses.
So, it is useful in treating HIRSUTISM besides being a K+ conserving diuretic.

• It is a Synthetic Steroid - a Competitive Antagonist of Aldosterone.

Question 14

MOA - antiandrogen…

Answer 14

MOA:
1) It inhibits 17α hydroxylase; thus it decreases testosterone biosynthesis.
2) It also blocks DHT receptors in the hair follicle - thus inhibiting the action of Testosterone at the hair follicles.
Therapeutic Uses:
• Treatment and management of Hirsutism.**
• Management of primary hyperaldosteronism.
• Antihypertensive – for volume overload hypertension.
• It is also a K+ Sparing Diuretic.

Question 15

flutamide and cyproterone

Answer 15

androgen and antian…

Both are Antiandrogens – DHT RECEPTOR BLOCKERS/Antagonists

Both are Antiandrogens – DHT RECEPTOR BLOCKERS/Antagonists
➢ Flutamide: A non-steroid – It is an Anilide.
Competes with DHT for intracellular androgen receptors and blocks the action of testosterone – it is a competitive DHT antagonist.**
The main adverse effect is – it is hepatotoxic.
Note: When flutamide and leuprolide are combined, there is a synergistic effect and there is no initial flare.
Use: Management of Prostate Cancer.
➢ Cyproterone acetate:
Antiandrogenic Steroid and it is also a most potent Progestin.
Blocks testosterone (DHT) Receptor.
Use of Cyproterone: To treat Hirsutism, To decrease Libido & aggressiveness in male sexual offenders. Note: Cyproterone acetate is a steroid - a potent Progesterone agonist (progestin) & an antiandrogen while flutamide is a non-steroid antiandrogen.

Question 16

glucocorticoids

Answer 16

Downregulate PLA2 (phospholipase A2) activity via proteins called Annexins – formerly called Lipocortins)

Decrease Cytokines and
the Release of Inflammatory Mediators: –
decrease ILs, PGs,
decrease LTs, NFκB.

↑ vasoconstriction &
↓ capillary permeability

Question 17

Different corticosteroid preparations

Answer 17

Primarily Glucocorticoid  (duration), (anti-inflm potency), (salt-retaining potency)
Cortisol 		 8-12	1		1
Prednisone	12-24	4	0.3	
Triamcinolone	15-24	5	0
Dexamethasone24-36	30		0

Primarily Mineralocorticoid
Aldosterone 1-2 0.3 3000
Fludrocortisone 8-12 10 125-250

Question 18

fludrocortisol

Answer 18

Fludrocortisol is a much more potent mineralocorticoid but has corticoteroid antiinflammatory activity – only used as a topical anti-inflammatory agent. It can be given orally to treat Addison’s Disease and for Orthostatic Hypotension. XXX

Question 19

corticosteroid administration

Answer 19

Corticosteroids: Administration,
Therapeutics
• Routes of Administration of various Corticosteroids.
• Cortisol is reserved for Replacement Therapy in
Primary Adrenocortical Failure - Addison’s Disease
or in adrenal biosynthetic Enzyme Defects that lead to Adrenal Hyperplasia as ACTH secretion is high With NO endogenous Cortisol Production and release.
• Rest of the Potent long acting synthetic corticosteroids are reserved for the management of severe forms of Inflammation, Autoimmune Diseases and for Immunosuppression.
• While Corticosteroids are important in the treatment of severe forms of inflammation & as an Immuno- suppressant, its long term treatment is accompanied by Iatrogenic Cushing Syndrome, the features of Excess Glucocorticoid activity elaborated in the next slide.
• It also leads to prolonged Suppression of ACTH. So, do slow tapered withdrawal of corticosteroids and do not over-treat the patient for prolonged periods.

Question 20

Glucocorticoids: Addison’s Disease

Answer 20

Treatment: Oral: Hydrocortisone, Prednisone or Fludrocortisol.
In severe Addisionian Crisis give cortisol hemisuccinate i.v. for rapid onset of action to recover the patient from shock and hypotensive collapse.
For Non-endocrine diseases, potent Corticosteroids are given:
i) Severe Inflammation,
ii) As Immunosuppressant,
iii) Management of autoimmune diseases,
iv) Severe asthma – status asthmaticus
v) Myeloproliferative diseases.
vi) Control Nausea & Vomiting when other agents fail
vii) Overcoming sickness at High Altitude.

Question 21

Corticosteroid Antagonists - (I) Receptor Antagonists XX

Answer 21

• Spironolactone:
– an antagonist of aldosterone at its receptor:
– Rx - Hypertension, Hirsutism, a K+ Cons. Diuretic.
• Mifepristone (RU 486): Steroid Competitive Antagonist.
– acts as an antagonist at both Glucocorticoid & Progesterone receptors.
– Considered for treatment of Cushing’s syndrome.
– Effective First Trimester Termination of Pregnancy.

Question 22

Corticosteroid Synthesis Inhibitors (II) XXX

Synthesis Inhibitors:

Answer 22

Used in the treatment of adrenal cancer when surgical therapy is impractical or unsuccessful because of metastases.
• 1. Ketoconazole (an antifungal agent):
– inhibits cytochrome P450 enzymes, therefore inhibiting the
synthesis of all steroids both gluoco and mineralocorticoid.
– used to treat adrenal carcinoma, hirsutism, breast cancer.
• 2. Aminoglutethimide:
blocks the conversion of cholesterol to pregnenolone, the rate limiting step, it inhibits the synthesis of all steroids.
• 3. Metyrapone:– an inhibitor of 11-b hydroxylase decrease Cortisol
Note: Mitotane –– an insecticide analogue of DDD
Destroys Adrenocortical cells. Helpful in the management
of inoperable Adrenal adenocarcinoma.

Question 23

Insulin sensitizers

Answer 23

Insulin Sensitizers
1. Biguanide – metformin
2. Thiazolidine Diones (TZD) – pioglitazone, rosiglitazone
Insulin Secretagogues
3. KATP Blockers – Sulfonylureas – glyburide; metiglinides – repaglinide
4. GLP-1 Analogs – Incretins Exanitide, Liraglutide
5. DPP4 inhibitor – Sitagliptin, saxagliptin
Insulin and ITS Analogs
6. Fast Acting: I-Lispro, I Aspart, I glusine; Short Acting: Regular Insulin; Intermediate: NPH Insulin; Long Acting: I-Glargine, I-Detemir
OTHER (NOT INSULIN)
7. Alpha-Glucosidase inhibitor – acarbose
8. SGLT2 – inhibitor – renal sodium-glucose co-transporter-2 inhibitor - dapagliflozin
WHO ESSENTIAL MEDICINE STATUS METFORMIN, GLYBURIDE, NPH-Insulin

Question 24

insulin preparations: onset and duration of activity

Answer 24

rapid acting
ONSET (HRS) PEAK (HRS) DURATION (HRS) COMMENTS
lispro insulin - 0.25; 1; 2-3; no rapid acting insulin should be used intravenously - rapid action is a result of rapid release from subcutaneous tissues
Insulin Aspart - 0.25; 1; 2-3
Glulisine - 0.25; 1; 2-3 - approved, to be marketed shortly

Short-acting
ONSET (HRS) PEAK (HRS) DURATION (HRS) COMMENTS
regular human insulin- 0.5-1; 2-4; 4-6; longer action if larger dose (mass action effect)

Intermediate-acting
ONSET (HRS) PEAK (HRS) DURATION (HRS) COMMENTS
NPH human - 0.5-1; 4-6; 8-16; peak and duration quite variable (neutral protamine hagedorn)

long acting
ONSET (HRS) PEAK (HRS) DURATION (HRS) COMMENTS
Insulin Glargine - 0.5-1; none; 23-26; basal insulin-minimal or no peak - cannot be mixed iwth other insulins - clear insulin forms crystals at in vivo pt.

Question 25

what are two types of therapies for insulin?

Answer 25

• Intensive Insulin Therapy: (Current Trend)
Basal insulin (Intermediate or Long-acting preparations: Glargine, Detemir or Degludec plus adjustable doses of pre-meal quick onset short and rapid-acting insulin analogs (Lispro, Aspart, or Glulisine) is the best approach to maintain steady state plasma euglycemic levels.
Lesser Incidence of Diabetic Complications.
• Conventional Insulin Therapy: (in the Past)
Twice-daily injections of short-acting (regular) and intermediate-acting insulin.
This regimen is not physiological and is no longer recommended as shown in the next slide

Conventional vs. Intensive Insulin Therapy XXX
Incidence of CV Events & Retinopathy is lower following Intensive Insulin Therapy

Question 26

Whata re the hazards of insulin use?

Answer 26

Hazards of Insulin Use
• Hypoglycemia (Insulin Shock)
– tachycardia, confusion, vertigo, diaphoresis,
– brain damage may occur
– Treatment: Prompt administration of glucose (sugar or candy by mouth, glucose -i.v.)
or glucagon (by intramuscular injection)
• Insulin-induced immunologic complications
– formation of insulin antibodies - insulin resistance particularly with modified insulins.
• Daily s.c. Admin. Painful, Lipodystrophy,
Edema/Weight Gain.

Question 27

sulfonylureas

Answer 27

insulin secretagogue - stimulate release of endogenous insulin

• 1st generation: [Not used]
• 2nd Generation: Glyburide (Diabeta), Glipizide,
• 3rd Generation: Glimepiride (Amaryl)
• 2nd and 3rd Generation Drugs: more potent, Long Acting, Better Pharmacokinetics, Less Adverse effects.
o Mechanism
• inhibit K+ATP channels in β-cell membrane
• Decrease Glucagon secretion
• may also increase the number of functional insulin receptors in peripheral tissues.
o Adverse Effects: Hypoglycemia, Rash, Allergic Reactions,
Nausea, Vomiting, Cholestatic Jaundice (lesser in 2nd & 3rd G).

Question 28

repaglinide (gluconorm)

Answer 28

insulin secretagogue - new compound from a chemical class know as miglitinides
•	Effects and mechanisms: same as Sufonylureas
–	stimulate the release of endogenous insulin
–	inhibit K+ATP channels on β-cell membrane
•	Ineffective in patients who lack functional β-cells or in advanced stages of Type II DM 
–	Repaglinide - rapid onset and short action; taken just before meals for controlling postprandial glucose concentrations when hypoglycemia is an issue with Sufonylureas

Question 29

biguanide: metformin (glucophage)

Answer 29

insulin secretagogue - • Reduce postprandial and fasting glucose in T2DM
• Mechanism
– Reduction of hepatic Gluconeogenesis, best agent for Type II
– Stimulation of glycolysis in peripheral tissues, AMPK activation mimics causes glucose utilization during exercise.
– reduction of glucose absorption from gastrointestinal tract
• Does NOT stimulate insulin Release from β-cells.
• Advantages: Safe drug exercise caution using it in renal failure patients
– Does not cause hypoglycemia (unlike sulfonylureas)
– no weight gain, less expensive, safety profile high, renal clearance, Useful for IR, Polycystic Ovary Synd., NAFLD XX .
• Adverse Effects
– GI Distress, (nausea, diarrhea, flatulence, cramps)
– Lactic Acidosis - especially in patients with renal or liver disease, alcoholism, or conditions that predispose to tissue anoxia.
BIGUANIDEs: METFORMIN decrease Plasma Glucose by decreaseing Hepatic Glucose Production by Improving Insulin Sensitivity XX
• Avoid giving this agent in patients with Renal Failure/liver failure.
• Also Helpful in Treating Insulin Resistance & Polycystic Ovarian Syndrome, Gestational Diabetes.
• In hypoxic condition its increased use may promote Lactic acidosis and accompanying muscle fatigue.

Question 30

Thiazolidinediones (TZD)

Answer 30

insulin secretagogue - TZD: Troglitazone (Rezulin) – not used, Rosiglitazone (Avandia), Pioglitazone (Acarbos) Not popular anymore
• Mechanism: Effective in HbA1C Control
– activate peroxisome proliferator activator receptor-gamma (PPAR-γ Activation)
– regulates the transcription of genes encoding proteins involved in carbohydrate and lipid metabolism.
– Were very, very popular between 1995-2007 - not anymore
– reduce both FPG and PPG levels - decrease hyperglycemia.
– Troglitazone – Heptatoxic hence it was withdrawn
– Rosiglitazone: ⎡MI, CV Risk, Hip Fracture, Anemia, Edema
– Pioglitazone Redistribution of fat to subcutaneous region.
– They are Contraindicated in Congestive Heart Failure.

Question 31

α-glucosidase inhibitor - Acarbose (Prandase)

Answer 31

• Mechanism and effects
– inhibits α-glucosidase in the gut, an enzyme necessary for the conversion of complex starches, oligosaccharides, and disaccharides to the monosaccharides that can be transported out of the intestinal lumen and into the bloodstream.
– slows absorption of carbohydrates
– reduces postprandial hyperglycemia
– has no effect on fasting blood sugar
• Used as monotherapy or in combination with other oral antidiabetic drugs (OADs)
• Adverse effects: Flatulence, Diarrhea, Cramping.

Question 32

glucagon like peptide (GLP-1) from GIT

Answer 32

insulin secretagogue - • GLP-1 Mimetics (injectable) / GLP-1 Analogs – Peptides not popular
– Exenatide
– Exenatide LAR
– Liraglutide NOT POPULAR now; Immunologic reactions!!
– Incretin Enhancers (DPP-4 inhibitors) are synthetic orally effective
– Sitagliptin* SITAGLIPTIN (Januvea)
– Vildagliptin
– Saxagliptin* (Onglyza)
– Alogliptin
*currently available in Canada
Sitagliptin, a DPP-4 Inhibitor, decreases the breakdown of endogneous GLP-1 (incretins level) promoting Increased insulin release, decrease glucagon production, reduced food intake, delayed gastirc emptying. All these lead to reduce hyperglycemia.

Question 33

DPP-4 inhibitors - sitagliptin

Answer 33

Mechanism of action - Inhibit degradation of Incretins (e.g., GLP-1) resulting in:
• Increases Insulin Release
• Decreases Glucagon secretion
• Delays Gastric Emptying
• Reduces Food Intake
Route of admin: oral
Potential Benefits over Exenatide and Liraglutide - Preservation or restoration of Beta-Cell Function, Durable Glucose Control, GLP-1 Peptide agonists Exenatide was given by parenteral and it becomes refractory due to antigenicity/antibody production.

Question 34

SGLT2-inhibitor - dapagliflozin

Answer 34

insulin secretagogue - • Much of the Glucose presented to the Kidney by Glomerular Filtration is Reabsorbed in the Proximal Convoluted Tubules (PCT) by Sodium-Glucose CO-Transporter (SGLT2).
• Once this is inhibited, Glycosuria occurs.
• Normoglycemia is restored.
• Euglycemia (normal blood sugar) restores Insulin release and Increased target site Insulin sensitivity.
• ADVANTAGES
• Decreased FBG & PPG (0.8 % decrease HbAIC (blood glucose).
• Lack of Hypoglycemia.
• Reduced Glucotoxicity
• Good Glycemic Control.
• Effective in Type II DM.
• They do not cause Weight Gain.
• Can Reduce Insulin Dose ( Increase Insulin Sensitivity).
• Increase Insulin Secretion.
• DISADVANTAGES
• Increased Incidence of Glycosuria.
• Large increase in Incidence of Genital Infections.
• Increased Urinary Tract Infections?
• Effect is Indirect.

Question 35

No Single Class of Oral Antihyperglycemic Monotherapy Targets
All Key Pathophysiologies

Answer 35

The early, aggressive approach to type 2 diabetes management avoids the risk of early treatment failure by adopting an intensive therapeutic strategy immediately upon diagnosis.
Combinations of agents with complementary modes of action targeting the dual defects underlying type 2 diabetes (insulin resistance and b-cell dysfunction) are most likely to support tight, long-term glycemic control.
Furthermore, combination therapy should be considered earlier in the regimen to provide additional glycemic control.

Question 36

Type II diabetes mellitus treatment

Answer 36

Class I - Insulin
Secretagogues
(Glyburide, Repaglinide)
#2. Biguanides
(METFORMIN)
#3. Thiazolidinediones (TZD)
(Rosiglitazone, Pioglitazone)
#4. α-glucosidase
Inhibitor (Acarbose)
New Additions: (2010):
Class #5. Dipeptidyl Peptidase-4 Inhibitor (DPP 4-I) Sitagliptin
Class #6. Sodium Glucose Co-Transport Inhibitor (SGLT2-I)
Dapagliflozin, Sergiflozin

Question 37

adverse effects to remember from diabetes lecture

Answer 37

Insulin: Sweating, Hypoglycemia, Weight Gain, Visual disturbances, Lipodystrophy, Allergic Reactions
Sulfonylureas - Glyburide: GI Disturbances, Hypoglycemia
Repaglinide: Drug levels altered when taken with other agents
Biguanides - Metformin: Lactic Acidosis, GI Disturbances.
Thaizolidinediones: Rosiglitazone: increase MI, Heart Attack, Potential CV Events, Edema, Hip Fracture, Redistribution of fat.
a -Glucosidase Inhibitor. Acarbose:
Abdominal pain, diarrhea, Flatulence, Malabsorption of Ca2+, iron, Thyroid hormones, several drugs and vitamins.
DPP-IV I: Sitagliptin: Nausea, GI Disturbances?
SGL-T2 Inhibitors: Glycosuria - increase Incidence of Genital& UT Infection.