- Describe and then refute the key points of the opposing view.
- Restate and reinforce the thesis and supporting evidence.
2. Drafting the Persuasive Essay
When writing the initial draft of a persuasive essay, consider the following suggestions:
- The introductory paragraph should have a strong “hook” that grabs the reader’s attention. Open with an unusual fact or statistic, a question or quotation, or an emphatic statement. For example: “Driving while talking on a cell phone, even hands-free, is the equivalent of driving drunk.”
- The thesis statement should leave no doubts about the writer’s position.
- Each body paragraph should cover a separate point, and the sentences of each paragraph should offer strong evidence in the form of facts, statistics, quotes from experts, and real-life examples.
The Secret to Good Paragraph Writing
- Consider various ways to make the argument, including using an analogy, drawing comparisons, or illustrating with hypothetical situation (e.g., what if, suppose that…).
- Don’t assume the audience has in-depth knowledge of the issue. Define terms and give background information.
- The concluding paragraph should summarize the most important evidence and encourage the reader to adopt the position or take action. The closing sentence can be a dramatic plea, a prediction that implies urgent action is needed, a question that provokes readers to think seriously about the issue, or a recommendation that gives readers specific ideas on what they can do.
3. Revising the Persuasive Essay
In the revision phase, students review, modify, and reorganize their work with the goal of making it the best it can be. Keep these considerations in mind:
- Does the essay present a firm position on the issue, supported by relevant facts, statistics, quotes, and examples?
- Does the essay open with an effective “hook” that intrigues readers and keeps them reading?
- Does each paragraph offer compelling evidence focused on a single supporting point?
- Is the opposing point of view presented and convincingly refuted?
- Is the sentence structure varied? Is the word choice precise? Do the transitions between sentences and paragraphs help the reader’s understanding?
- Does the concluding paragraph convey the value of the writer’s position and urge the reader to think and act?
If the essay is still missing the mark, take another look the thesis. Does it present the strongest argument? Test it by writing a thesis statement for the opposing viewpoint. In comparison, does the original thesis need strengthening? Once the thesis presents a well-built argument with a clear adversarial viewpoint, the rest of the essay should fall into place more easily.
4. Editing the Persuasive Essay
Next, proofread and correct errors in grammar and mechanics, and edit to improve style and clarity. Having a friend read the essay helps writers edit with a fresh perspective.
5. Publishing the Persuasive Essay
Sharing a persuasive essay with the rest of the class or with family and friends can be both exciting and intimidating. Learn from the experience and use the feedback to make the next essay even better.
Time4Writing Teaches Persuasive Essay Writing
Time4Writing essay writing courses offer a highly effective way to learn how to write the types of essays required for school, standardized tests, and college applications. These online writing classes for elementary, middle school, and high school students, break down the writing process into manageable chunks, easily digested by young writers. Students steadily build writing skills and confidence with each online writing course, guided by one-on-one instruction with a dedicated, certified teacher. We first introduce essay writing to students at the elementary level, with our Beginning Essay Writing course, where they will have an opportunity to write their first five-paragraph essay. Our middle school online writing courses, Welcome to the Essay and Advanced Essay, teach students the fundamentals of writing essays, including the persuasive essay. The high school online writing class, Exciting Essay Writing, focuses in depth on the essay writing process with preparation for college as the goal. Time4Writing’s online writing classes for kids also cover how to interpret writing prompts in testing situations. Read what parents are saying about their children’s progress with Time4Writing’s online writing courses.
Acarbose is a complex oligosaccharide that delays the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. As a consequence of plasma glucose reduction, PRECOSE reduces levels of glycosylated hemoglobin in patients with type 2 diabetes mellitus. Systemic non-enzymatic protein glycosylation, as reflected by levels of glycosylated hemoglobin, is a function of average blood glucose concentration over time.
Mechanism of Action
In contrast to sulfonylureas, PRECOSE does not enhance insulin secretion. The antihyperglycemic action of acarbose results from a competitive, reversible inhibition of pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolase enzymes. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine, while the membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. In diabetic patients, this enzyme inhibition results in a delayed glucose absorption and a lowering of postprandial hyperglycemia.
Because its mechanism of action is different, the effect of PRECOSE to enhance glycemic control is additive to that of sulfonylureas, insulin or metformin when used in combination. In addition, PRECOSE diminishes the insulinotropic and weight-increasing effects of sulfonylureas.
Acarbose has no inhibitory activity against lactase and consequently would not be expected to induce lactose intolerance.
In a study of 6 healthy men, less than 2% of an oral dose of acarbose was absorbed as active drug, while approximately 35% of total radioactivity from a 14C-labeled oral dose was absorbed. An average of 51% of an oral dose was excreted in the feces as unabsorbed drug-related radioactivity within 96 hours of ingestion. Because acarbose acts locally within the gastrointestinal tract, this low systemic bioavailability of parent compound is therapeutically desired. Following oral dosing of healthy volunteers with 14C-labeled acarbose, peak plasma concentrations of radioactivity were attained 14–24 hours after dosing, while peak plasma concentrations of active drug were attained at approximately 1 hour. The delayed absorption of acarbose-related radioactivity reflects the absorption of metabolites that may be formed by either intestinal bacteria or intestinal enzymatic hydrolysis.
Acarbose is metabolized exclusively within the gastrointestinal tract, principally by intestinal bacteria, but also by digestive enzymes. A fraction of these metabolites (approximately 34% of the dose) was absorbed and subsequently excreted in the urine. At least 13 metabolites have been separated chromatographically from urine specimens. The major metabolites have been identified as 4-methylpyrogallol derivatives (that is, sulfate, methyl, and glucuronide conjugates). One metabolite (formed by cleavage of a glucose molecule from acarbose) also has alpha-glucosidase inhibitory activity. This metabolite, together with the parent compound, recovered from the urine, accounts for less than 2% of the total administered dose.
The fraction of acarbose that is absorbed as intact drug is almost completely excreted by the kidneys. When acarbose was given intravenously, 89% of the dose was recovered in the urine as active drug within 48 hours. In contrast, less than 2% of an oral dose was recovered in the urine as active (that is, parent compound and active metabolite) drug. This is consistent with the low bioavailability of the parent drug. The plasma elimination half-life of acarbose activity is approximately 2 hours in healthy volunteers. Consequently, drug accumulation does not occur with three times a day (t.i.d.) oral dosing.
The mean steady-state area under the curve (AUC) and maximum concentrations of acarbose were approximately 1.5 times higher in elderly compared to young volunteers; however, these differences were not statistically significant. Patients with severe renal impairment (Clcr < 25 mL/min/1.73m²) attained about 5 times higher peak plasma concentrations of acarbose and 6 times larger AUCs than volunteers with normal renal function. No studies of acarbose pharmacokinetic parameters according to race have been performed. In U.S. controlled clinical studies of PRECOSE in patients with type 2 diabetes mellitus, reductions in glycosylated hemoglobin levels were similar in Caucasians (n=478) and African-Americans (n=167), with a trend toward a better response in Latinos (n=132).
Studies in healthy volunteers have shown that PRECOSE has no effect on either the pharmacokinetics or pharmacodynamics of nifedipine, propranolol, or ranitidine. PRECOSE did not interfere with the absorption or disposition of the sulfonylurea glyburide in diabetic patients. PRECOSE may affect digoxin bioavailability and may require dose adjustment of digoxin by 16% (90% confidence interval: 8-23%), decrease mean Cmax of digoxin by 26% (90% confidence interval: 16–34%) and decreases mean trough concentrations of digoxin by 9% (90% confidence limit: 19% decrease to 2% increase). (See PRECAUTIONS: DRUG INTERACTIONS.)
The amount of metformin absorbed while taking PRECOSE was bioequivalent to the amount absorbed when taking placebo, as indicated by the plasma AUC values. However, the peak plasma level of metformin was reduced by approximately 20% when taking PRECOSE due to a slight delay in the absorption of metformin. There is little if any clinically significant interaction between PRECOSE and metformin.
Clinical Experience from Dose Finding Studies in Type 2 Diabetes Mellitus Patients on Dietary Treatment Only
Results from six controlled, fixed-dose, monotherapy studies of PRECOSE in the treatment of type 2 diabetes mellitus, involving 769 PRECOSE-treated patients, were combined and a weighted average of the difference from placebo in the mean change from baseline in glycosylated hemoglobin (HbA1c) was calculated for each dose level as presented below:
|Mean Placebo-Subtracted Change in HbA1c in Fixed-Dose Monotherapy Studies|
|Dose of PRECOSE*||N||Change in HbA1c %||p-Value|
|25 mg t.i.d.||110||-0.44||0.0307|
|50 mg t.i.d.||131||-0.77||0.0001|
|100 mg t.i.d.||244||-0.74||0.0001|
|200 mg t.i.d.**||231||-0.86||0.0001|
|300 mg t.i.d.**||53||-1||0.0001|
|* PRECOSE was statistically significantly different from placebo at all doses. Although there were no statistically significant differences among the mean results for doses ranging from 50 to 300 mg t.i.d., some patients may derive benefit by increasing the dosage from 50 to 100 mg t.i.d.|
Although studies utilized a maximum dose of 200 or 300 mg t.i.d., the maximum recommended dose for patients < 60 kg is 50 mg t.i.d.; the maximum recommended dose for patients > 60 kg is 100 mg t.i.d.
Results from these six fixed-dose, monotherapy studies were also combined to derive a weighted average of the difference from placebo in mean change from baseline for one-hour postprandial plasma glucose levels as shown in the following figure:
* PRECOSE was statistically significantly different from placebo at all doses with respect to effect on one-hour postprandial plasma glucose.
**The 300 mg t.i.d. PRECOSE regimen was superior to lower doses, but there were no statistically significant differences from 50 to 200 mg t.i.d.
Clinical Experience in Type 2 Diabetes Mellitus Patients on Monotherapy, or in Combination with Sulfonylureas, Metformin or Insulin
PRECOSE was studied as monotherapy and as combination therapy to sulfonylurea, metformin, or insulin treatment. The treatment effects on HbA1c levels and one-hour postprandial glucose levels are summarized for four placebo-controlled, double-blind, randomized studies conducted in the United States in Tables 2 and 3, respectively. The placebo-subtracted treatment differences, which are summarized below, were statistically significant for both variables in all of these studies.
Study 1 (n=109) involved patients on background treatment with diet only. The mean effect of the addition of PRECOSE to diet therapy was a change in HbA1c of -0.78%, and an improvement of one-hour postprandial glucose of -74.4 mg/dL.
In Study 2 (n=137), the mean effect of the addition of PRECOSE to maximum sulfonylurea therapy was a change in HbA1c of -0.54%, and an improvement of one-hour postprandial glucose of -33.5 mg/dL.
In Study 3 (n=147), the mean effect of the addition of PRECOSE to maximum metformin therapy was a change in HbA1c of -0.65%, and an improvement of one-hour postprandial glucose of -34.3 mg/dL.
Study 4 (n=145) demonstrated that PRECOSE added to patients on background treatment with insulin resulted in a mean change in HbA1c of -0.69%, and an improvement of one-hour postprandial glucose of -36.0 mg/dL.
A one year study of PRECOSE as monotherapy or in combination with sulfonylurea, metformin or insulin treatment was conducted in Canada in which 316 patients were included in the primary efficacy analysis (Figure 2). In the diet, sulfonylurea and metformin groups, the mean decrease in HbA1c produced by the addition of PRECOSE was statistically significant at six months, and this effect was persistent at one year. In the PRECOSE-treated patients on insulin, there was a statistically significant reduction in HbA1c at six months, and a trend for a reduction at one year.
Table 2: Effect of Precose on HbA1c
|Mean Baseline||Mean change from baselineb||Treatment Difference|
|1||Placebo Plus Diet||8.67||0.33||—||—|
|PRECOSE 100 mg t.i.d. Plus Diet||8.69||-0.45||-0.78||0.0001|
|2||Placebo Plus SFUc||9.56||0.24||—||—|
|PRECOSE 50–300d mg t.i.d. Plus SFUc||9.64||-0.3||-0.54||0.0096|
|3||Placebo Plus Metformine||8.17||+0.08 g||—||—|
|PRECOSE 50–100 mg t.i.d. Plus Metformine||8.46||-0.57 g||-0.65||0.0001|
|4||Placebo Plus Insulinf||8.69||0.11||—||—|
|PRECOSE 50–100 mg t.i.d. Plus Insulinf||8.77||-0.58||-0.69||0.0001|
|aHbA1c Normal Range: 4–6% |
bAfter four months treatment in Study 1, and six months in Studies 2, 3, and 4
cSFU, sulfonylurea, maximum dose
dAlthough studies utilized a maximum dose of up to 300 mg t.i.d., the maximum recommended dose for patients ≤ 60 kg is 50 mg t.i.d.; the maximum recommended dose for patients > 60 kg is 100 mg t.i.d.
eMetformin dosed at 2000 mg/day or 2500 mg/day
fMean dose of insulin 61 U/day
gResults are adjusted to a common baseline of 8.33%
Table 3: Effect of Precose on Postprandial Glucose
|Study||Treatment||One-Hour Postprandial Glucose (mg/dL)||p-Value|
|Mean Baseline||Mean change from baselinea||Treatment Difference|
|1||Placebo Plus Diet||297.1||31.8||—||—|
|PRECOSE 100 mg t.i.d. Plus Diet||299.1||-42.6||-74.4||0.0001|
|2||Placebo Plus SFUb||308.6||6.2||—||—|
|PRECOSE 50–300c mg t.i.d. Plus SFUb||311.1||-27.3||-33.5||0.0017|
|3||Placebo Plus Metformind||263.9||+3.3f||—||—|
|PRECOSE 50–100 mg t.i.d. Plus Metformind||283||-31.0f||-34.3||0.0001|
|4||Placebo Plus Insuline||279.2||8||—||—|
|PRECOSE 50–100 mg t.i.d. Plus Insuline||277.8||-28||-36||0.0178|
|aAfter four months treatment in Study 1, and six months in Studies 2, 3, and 4 |
bSFU, sulfonylurea, maximum dose
cAlthough studies utilized a maximum dose of up to 300 mg t.i.d., the maximum recommended dose for patients ≤ 60 kg is 50 mg t.i.d.; the maximum recommended dose for patients > 60 kg is 100 mg t.i.d.
dMetformin dosed at 2000 mg/day or 2500 mg/day
eMean dose of insulin 61 U/day
fResults are adjusted to a common baseline of 273 mg/dL
Figure 2: Effects of PRECOSE (III ) and Placebo ( III ) on mean change in HbA1c levels from baseline throughout a one-year study in patients with type 2 diabetes mellitus when used in combination with: (A) diet alone; (B) sulfonylurea; (C) metformin; or (D) insulin. Treatment differences at 6 and 12 months were tested: * p < 0.01; # p = 0.077.