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WorksheetsDiabetes pt 2 and Estrogen and Progesterone Agents
Total questions: 60
Worksheet time: 30mins
According to treatment guidance, initial combination therapy should be considered when A1C is:
0.5% above target
1% above target
1.5–2.0% above target
3.0% above target
Which medication combination should NOT be used together?
SGLT2 inhibitor + GLP-1 receptor agonist
Metformin + SGLT2 inhibitor
Sulfonylurea + insulin
GLP-1 agonist + TZD
Which therapy class is recommended for cardiorenal risk reduction, relevant in MASLD management?
DPP-4 inhibitors
Sulfonylureas
GLP-1 receptor agonists & SGLT2 inhibitors
TZDs only
Which of the following is a common trigger for DKA or HHS?
Chronic stable exercise
Missed insulin doses
Metformin initiation
Carbohydrate-restricted diet
Which treatment is shared in both DKA and HHS management?
IM glucagon
High-dose IV insulin only
IV fluids + electrolytes + insulin
DPP-4 inhibitor therapy
According to ADA treatment recommendations, medication regimens and adherence should be reassessed at what interval to avoid delays in intensification?
Every month
Every 3–6 months
Once annually
Only when A1C rises by ≥2%
Which combination reflects a contraindicated/avoid pairing?
GLP-1 agonist + SGLT2 inhibitor
Metformin + GLP-1 agonist
GLP-1 agonist + DPP-4 inhibitor
TZD + SGLT2 inhibitor
When managing diabetes, treatment goals must address both glycemic and which additional clinical domain?
Hepatic fibrosis score
Immunization compliance
Weight management
Hospital readmission rate
A patient using metformin monotherapy remains above A1C goal after 3 months of adherence. According to treatment guidance, what is the next appropriate step?
Increase monitoring frequency but delay therapy change
Add an additional agent based on comorbid needs
Switch to insulin immediately
Repeat A1C in 12 months
Which of the following is prioritized for type 2 diabetes patients with ASCVD or high ASCVD risk?
Sulfonylureas
GLP-1 receptor agonists or SGLT2 inhibitors
DPP-4 inhibitors alone
TZDs alone
Which patient profile is the best match for insulin pump therapy?
Performs SMBG <2 times daily
Motivated and checks glucose ≥4 times daily
Refuses diabetes self-management training
Only requires basal insulin
A 59-year-old patient with T2DM on metformin and lifestyle modification continues to have an A1C above goal. BMI is 35 kg/m². No ASCVD, CKD, or HF. She asks for medication that will help with glucose AND weight and wants to avoid hypoglycemia.
Which is the best next step?
Add sulfonylurea
Add GLP-1
Begin basal insulin
Add DPP-4 inhibitor
A 63-year-old patient has T2DM, obesity, and suspected MASLD based on elevated ALT and ultrasound findings. Which diabetes therapy class supports liver-related AND cardiorenal benefits?
DPP-4 inhibitors
SGLT2 inhibitor
Sulfonylureas
Regular insulin
A 42-year-old patient presents with recent unintentional weight loss, elevated glucose, and symptoms of polyuria and polydipsia. Current therapy is metformin only.
Which recommendation aligns with guidelines?
Increase metformin to maximum dose
Add GLP-1 RA and reassess in 6 months
Start insulin due to catabolic state
Begin DPP-4 inhibitor
Which statement best describes the link between diabetes treatment and MASLD management?
Hepatic outcomes improve only with insulin
Therapies that improve metabolic and cardiac risk are preferred
MASLD treatment is not affected by diabetes therapy choice
DPP-4 inhibitors are the first-line medication for MASLD
A patient is newly diagnosed with diabetes after showing elevated A1C and symptoms of hyperglycemia. They also have obesity and elevated ASCVD risk. After metformin, which therapy class best aligns with pathophysiology, weight benefit, and cardiometabolic protection?
Sulfonylurea
GLP-1
Regular insulin
Premixed insulin
A T2DM patient with persistent hyperglycemia despite basal insulin has post-meal elevations. Which adjustment best aligns with both intensification strategy and DKA prevention?
Increase basal insulin dose only
Add rapid-acting insulin at meals
Switch to DPP-4 inhibitor monotherapy
Discontinue insulin and start SGLT2 inhibitor
A patient is experiencing possible DKA symptoms (polyuria, fatigue, abdominal pain) after missing insulin due to illness. Which treatment principle combines acute management and pathophysiologic correction?
Rehydrate and initiate IV fluids, electrolytes, and insulin
Administer sliding-scale insulin and restrict fluids
Start oral antihyperglycemics
Increase carbohydrate intake
A patient using a GLP-1 RA + metformin still has A1C above goal after 6 months. Which next step aligns with treatment reassessment frequency, insulin strategy, and hypoglycemia risk minimization?
Continue current therapy without change
Reassess and consider adding basal insulin
Add DPP-4 inhibitor for incretin synergy
Switch directly to premixed insulin
A patient is on metformin and basal insulin, but A1C remains elevated due to post-prandial hyperglycemia. Which adjustment aligns with insulin kinetics, intensification principles, and hyperglycemia crisis prevention?
Increase basal dose by 10–20%
Add rapid-acting mealtime insulin
Switch to NPH at bedtime
Discontinue insulin and use DPP-4 inhibitor instead
A 57-year-old with T2DM is on metformin 1000 mg BID and glargine 28 units QHS. Fasting glucose averages 95–115 mg/dL, but post-meal readings remain 220–260 mg/dL. A1C is still above goal.
Which adjustment is most appropriate?
Increase glargine to 40 units nightly
Add rapid-acting insulin before the largest meal
Switch glargine to NPH BID
Add sulfonylurea
A 42-year-old has severe hyperglycemia, polyuria, recent 12-lb weight loss, and ketones in urine.
Best action:
Start dual oral therapy
Start GLP-1 RA
Initiate insulin therapy immediately
Add DPP-4 inhibitor
A clinician wants to add sitagliptin to a patient already receiving dulaglutide.
Appropriate response:
Proceed to enhance incretin synergy
Avoid due to overlapping mechanism and limited benefit
Switch dulaglutide to basal insulin
Add SGLT2 inhibitor also
A patient’s TDD is 36 units/day.
What is the approximate CF (mg/dL drop per 1 unit of rapid-acting insulin)?
30 mg/dL/unit
40 mg/dL/unit
50 mg/dL/unit
60 mg/dL/unit
Current BG 275 mg/dL, target 110 mg/dL
CF = 1:50 mg/dL
How many correction units are needed?
1 unit
3 units
5 units
7 units
Which estrogen is considered the most potent endogenous estrogen in women?
Estriol
Estrone
Ethinyl estradiol
Estradiol
Which of the following correctly describes the carbon structure of estrogens and progestins?
Estrogens are C21 steroids; progestins are C18 steroids
Estrogens are C18 steroids; progestins are C21 steroids
Both are C19 steroids
Estrogens are C17 steroids; progestins are C20 steroids
Which of the following increases with estrogen therapy according to metabolic effects?
LDL
Bone resorption
HDL
Plasma antithrombin III
Which enzyme is responsible for converting androgens into estrogens?
17,20-lyase
Estradiol dehydrogenase
Aromatase
5-α reductase
Which estrogen formulation is a prodrug that undergoes hepatic O-demethylation to form ethinyl estradiol?
Estradiol valerate
Mestranol
Quinestrol
Sodium equilin sulfate
Which mechanism explains how estrogens exert their physiological action?
Bind cell surface G-protein coupled receptors
Activate tyrosine kinase receptors
Bind SHBG then act via nuclear receptors
Act only through membrane-bound receptors
Which adverse effect is specifically associated with unopposed estrogen therapy?
Venous ulcers
Endometrial carcinoma
Pulmonary fibrosis
Rheumatoid arthritis flare
What clinical effect results from the GI bacterial hydrolysis of EE conjugates?
Increased hepatic toxicity
Increased clearance of EE
Reabsorption and enhanced efficacy of EE
Increased protein binding and reduced activity
Which anti-estrogen competitively inhibits estrogen receptors and is used to treat anovulatory infertility?
Fulvestrant
Clomiphene
Ethinyl estradiol
Drospirenone
Which type of aromatase inhibitor is steroid-based and irreversible?
Triazole derivatives
Mestranol
Exemastane
Quinestrol
Which of the following describes the primary contraceptive mechanism of progesterone?
Inhibition of androgen synthesis
Suppression of GnRH → ↓ LH/FSH release
Increased endometrial proliferation
Blocking aromatase enzymes
Which of the following progesterone adverse effects occurs due to androgen receptor binding?
Osteoporosis
Hyperthyroidism
Acne and hirsutism
Hypoglycemia
Which progesterone agent is classified as a 19-nor progesterone derivative?
Norgestrel
Estradiol
Quinestrol
Equilin sulfate
Which phase of the menstrual cycle is primarily driven by estrogen-mediated endometrial rebuilding?
Secretory phase
Follicular (proliferative) phase
Luteal phase
Menstrual phase
Which estrogenic effect on bone contributes to decreased risk of osteoporosis?
Increased osteoclast proliferation
Stimulating osteoblast apoptosis
Promoting osteoclast apoptosis
Increased calcium excretion
Which factor makes ethinyl estradiol significantly more potent than estradiol?
Increased water solubility
C17 alkylation
Greater SHBG binding affinity
Reduced plasma half-life
Which of the following estrogens is derived from pregnant mares and used orally?
Estradiol valerate
Sodium equilin sulfate
Quinestrol
Estriol sulfate
Which of the following is TRUE regarding estrogen receptor subtypes?
ER-α is the only receptor activated by endogenous estrogens
Both ER-α and ER-β are G-protein coupled receptors
Both ER-α and ER-β are ligand-activated transcription factors
ER-β is only active during pregnancy
Which delivery system provides slow, sustained systemic estrogen levels with fewer peaks and troughs?
PR suppository estrone
Which statement best explains why antibiotics may reduce oral contraceptive efficacy?
They displace estrogen from SHBG
They inhibit liver conjugation enzymes
They destroy gut bacteria that hydrolyze conjugates needed for EE reabsorption
They increase estrogen renal excretion
Fulvestrant differs from clomiphene because it is described as:
A partial estrogen agonist
A pure estrogen receptor antagonist
An aromatase substrate
A triazole derivative
Which of the following causes menstruation at the end of the cycle?
Estrogen surge
Progesterone receptor saturation
Decline in both estrogen and progesterone levels
Aromatase inhibition
Which clinical use of progesterone is specifically related to patients taking estrogen in post-menopause?
Treating PMS
Reducing endometrial hyperplasia
Contraception
Treating vasomotor hot flashes
Which progesterone receptor isoforms exist and mediate genomic signaling?
PR-α and PR-γ
PR-α and PR-β
PR-A and PR-B
PR-B and PR-D
Which of the following endogenous estrogens is considered the weakest in potency?
Estradiol
Estrone
Estriol
Mestranol
Which estrogen structural feature is essential for estrogenic activity according to SAR?
C21 steroid backbone
Aromatic A-ring + C3 hydroxyl group
Alkyne at C17
Sulfation of estrone
Which estrogen source becomes the primary contributor in post-menopausal women?
Ovaries
Adrenal cortex
Placenta
Adipose tissue
Which adverse effect of estrogen is most directly linked to thromboembolism risk?
Increased HDL
Increase in clotting factors II, VII, IX, and X
Breast tenderness
Hyperpigmentation
Which anti-estrogen is indicated for tamoxifen-resistant breast cancer?
Clomiphene
Mestranol
Fulvestrant
Drospirenone
Which best describes the feedback effect of clomiphene on the HPO axis?
Enhances estrogen negative feedback
Blocks estrogen receptors → ↑ GnRH → ↑ LH/FSH
Direct inhibition of aromatase
Suppression of follicular development
Which progesterone-mediated reproductive effect is responsible for maintaining pregnancy?
Stimulation of endometrial proliferation
Transition to secretory endometrium + reduced uterine contractility
Inducing luteolysis
High-dose inhibition of implantation
Which drug has an aminoalkyl ether side chain important for its anti-estrogenic activity?
Drospirenone
Fulvestrant
Clomiphene
Equilin sulfate
Which adverse effect of progesterone is explained by its interaction with androgen receptors?
Osteoporosis
Vaginal dryness
Acne and hirsutism
Hypertension
What is the primary SAR purpose of adding an ethinyl (≡C–H) group at C17 to estradiol?
Increase receptor affinity only
Convert it into a prodrug
Prevent metabolic inactivation and increase oral potency
Increase water solubility for IV administration
Mestranol differs structurally from ethinyl estradiol due to which modification?
C17 esterification
C3 methylation (-OCH₃) forming a prodrug
Removal of aromaticity
Fluorination of the A ring
